tretinoin has been researched along with Bone-Resorption* in 31 studies
1 review(s) available for tretinoin and Bone-Resorption
1 trial(s) available for tretinoin and Bone-Resorption
30 other study(ies) available for tretinoin and Bone-Resorption
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Pilose antler (Cervus elaphus Linnaeus) polysaccharide and polypeptide extract inhibits bone resorption in high turnover type osteoporosis by stimulating the MAKP and MMP-9 signaling pathways.
Pilose antler is a traditional Chinese medicine used to improve kidney function, strengthen tendons and bones, and prolong life, among other uses. It is widely employed in the treatment of osteoporosis. However, the molecular mechanisms underlying the treatment of high turnover osteoporosis are not fully understood.. The present study aimed to investigate the molecular mechanism underlying pilose antler polysaccharide and polypeptide extracts in inhibiting bone resorption in high turnover osteoporosis, and compare the effects of the two components alone and in combination to explore whether they could produce synergistic enhancement effects.. The quantitative and qualitative characteristics of pilose antler polysaccharide and polypeptide extracts were detected by UV-visible spectrophotometry and high-performance liquid chromatography. A rat model of retinoic acid-induced osteoporosis was used to evaluate the inhibitory effect of the extracts on bone resorption. Enzyme-linked immunosorbent assay (ELISA) was used to detect the activity of factors related to high turnover type osteoporosis in rat serum. Western blotting was used to detect the expression of proteins related to the MAKP and MMP-9 signaling pathways in rat femurs. Fluorescence quantitative PCR was used to detect the transcription levels of genes related to the MAKP and MMP-9 signaling pathways in rat femur tissues. Hematoxylin and eosin staining were used to observe the osteoprotective effects of pilose antler polysaccharides and polypeptides.. The yield of pilose antler polysaccharides was 8.3%, and was mainly composed of mannose, glucosamine hydrochloride, glucuronic acid, Galacturonic acid, Galactose hydrochloride, glucose, and galactose. The yield of the polypeptides was 26.2%, and eighty percent of the molecular weight of the antler polypeptides was 1.6 kDa-7kD, among which, the molecular weight of 7kD peptide accounted for 52% of the total. Both polysaccharides and peptides could reduce the activities of TRACP, OCN, ERK1, JNK, and MMP-9 in rat serum and reduce both the protein expression and gene transcription levels of ERK1, JNK, and MMP-9 in rat femur tissue with significant differences compared with the model group. Both extracts exerted significant protective effects on rat femur tissue. The effect of pilose antler polypeptides alone was better than that of polysaccharides either alone or in combination.. Pilose antler polysaccharides, polypeptides, and their mixtures could inhibit the occurrence of bone resorption of high turnover osteoporosis by stimulating the MAKP and MMP-9 signaling pathways to reduce the expression of the ERK1, JNK, and MMP-9 genes and proteins, and could help alleviate bone loss caused by retinoic acid. Pilose antler polypeptides had a stronger effect on inhibiting bone resorption. The combination of the two components did not show synergistic enhancement effect, and the polysaccharide tended to moderate the inhibitory enhancement effect of the polypeptide. Topics: Animals; Bone Resorption; Deer; Galactose; Matrix Metalloproteinase 9; Osteoporosis; Peptides; Polysaccharides; Proteins; Rats; Signal Transduction; Tretinoin | 2023 |
Bisphenol A inhibits osteogenic activity and causes bone resorption via the activation of retinoic acid-related orphan receptor α.
Bisphenol A (BPA) has deleterious effects on bone metabolism; however, its underlying mechanism has not yet been comprehensively understood. Here, we investigated whether RORα plays an important role in BPA-induced bone resorption both in vitro and in vivo. We found that BPA (0.1-1 μM) inhibited osteogenic activity (including ALP activity and mineralization), decreased the expression levels of osteoblast markers (such as RUNX2, OSX, and ALP) in human MG-63 osteoblast-like osteosarcoma cells, and inhibited spontaneous vertebral formation in zebrafish larvae. Additionally, BPA diminished β-glycerophosphate-induced osteoblast differentiation and vertebral formation, while simultaneously downregulating the expression levels of RUNX2a, OSX, and ALP. Furthermore, molecular docking data showed that a hydroxyl group of BPA dominantly binds to the H3 (ALA70) and/or H5 (ARG107) of RORα-ligand binding domain with hydrogen bonding (ALA330 and/or ARG367 in the full length of RORα, respectively), which another hydroxyl group of BPA fits into H3, H6, and H7 elements with non-covalent interactions, resulting in the activation of RORα. However, an RORα inverse agonist potently inhibited BPA-induced anti-osteogenic activity and vertebral formation in zebrafish larvae, concomitant with inhibition of osteogenic gene expression. Overall, our findings reveal that BPA inhibits osteoblast differentiation and bone formation by activating RORα. These results suggest that BPA exposure (0.1-1 μM) can cause various bone-resorptive diseases, such as osteoporosis. Topics: Animals; Benzhydryl Compounds; Bone Resorption; Cell Differentiation; Humans; Molecular Docking Simulation; Osteogenesis; Phenols; Retinoic Acid Receptor alpha; Tretinoin; Zebrafish | 2022 |
RARγ is a negative regulator of osteoclastogenesis.
Vitamin A is known to influence post-natal bone content, with excess intake being associated with reduced bone mineral density and increased fracture risk. Despite this, the roles retinoids play in regulating osteoclastogenesis, particularly in vivo, remain unresolved. This study therefore aimed to determine the effect of loss of retinoic acid receptors (RAR)α or RARγ on bone mass (analyzed by histomorphometry and dual-energy X-ray absorptiometry) and osteoclastogenesis in mice in vivo. RARγ null mice had significantly less trabecular bone at 8 weeks of age compared to wildtype littermates. In contrast, no change in trabecular bone mass was detected in RARα null mice at this age. Further histomorphometric analysis revealed a significantly greater osteoclast surface in bones from 8-week-old RARγ null male mice. This in vivo effect was cell lineage autonomous, and was associated with increased osteoclastogenesis in vitro from hematopoietic cells obtained from 8-week-old RARγ null male mice. The use of highly selective agonists in RANKL-induced osteoclast differentiation of wild type mouse whole bone marrow cells and RAW264.7 cells in vitro showed a stronger inhibitory effect of RARγ than RARα agonists, suggesting that RARγ is a more potent inhibitor of osteoclastogenesis. Furthermore, NFAT activation was also more strongly inhibited by RARγ than RARα agonists. While RARα and RARγ antagonists did not significantly affect osteoclast numbers in vitro, larger osteoclasts were observed in cultures stimulated with the antagonists, suggesting increased osteoclast fusion. Further investigation into the effect of retinoids in vivo revealed that oral administration of 5mg/kg/day ATRA for 10 days protected against bone loss induced by granulocyte colony-stimulating factor (G-CSF) by inhibiting the pro-osteoclastogenic action of G-CSF. Collectively, our data indicates a physiological role for RARγ as a negative regulator of osteoclastogenesis in vivo and in vitro, and reveals distinct influences of RARα and RARγ in bone structure regulation. Topics: Animals; Bone and Bones; Bone Density; Bone Resorption; Cell Differentiation; Gene Expression Regulation, Neoplastic; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NFATC Transcription Factors; Osteoclasts; Primary Cell Culture; RANK Ligand; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Retinoic Acid Receptor gamma; Signal Transduction; Tretinoin | 2015 |
Retinoic acid induces two osteocalcin isoforms and inhibits markers of osteoclast activity in Atlantic cod (Gadus morhua) ex vivo cultured craniofacial tissues.
Nutritional status including vitamin A could explain some of the developmental deformities observed in cultivated teleosts, including Atlantic cod (Gadus morhua). In the present study we aimed to investigate the transcriptional effect of retinoic acid (RA) on bone related genes using Atlantic cod craniofacial explants tissue cultures. Two different osteoblast specific osteocalcin/bone gla protein isoforms were discovered in cod. Transcription of both isoforms was up-regulated following RA treatment of 65 dph cod lower jaw explants. In contrast, transcripts coding for genes related to bone resorption and osteoclast activity, matrix metalloproteinase 9 and cathepsin K were down-regulated following RA treatment. This could be linked to the decreased transcriptional ratio between receptor activator of nuclear factor kappa-B ligand rankl and osteoprotegerin observed in the same tissue samples. RA treatment of juvenile explants had no effect on runt-related transcription factor 2 and osterix mRNA levels. However, osterix was significantly down-regulated in 25 dph cod head explants following RA treatment. In situ hybridizations revealed differential spatial distribution of the two isoforms and the predominant expression of cathepsin K in bone surrounding tissues. The present study indicates that RA causes a shift in the balance between osteoclast activity and osteoblast activity in favor of the latter. Topics: Amino Acid Sequence; Animals; Base Sequence; Biomarkers; Bone Resorption; Cell Differentiation; Cluster Analysis; Face; Fish Proteins; Gadus morhua; Gene Expression Regulation; In Situ Hybridization; Molecular Sequence Data; Osteoblasts; Osteocalcin; Osteoclasts; Phylogeny; Protein Isoforms; Protein Transport; RNA, Messenger; Skull; Tissue Culture Techniques; Transcription, Genetic; Tretinoin | 2012 |
Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor.
Increased vitamin A (retinol) intake has been suggested to increase bone fragility. In the present study, we investigated effects of retinoids on bone resorption in cultured neonatal mouse calvarial bones and their interaction with glucocorticoids (GC). All-trans-retinoic acid (ATRA), retinol, retinalaldehyde, and 9-cis-retinoic acid stimulated release of (45)Ca from calvarial bones. The resorptive effect of ATRA was characterized by mRNA expression of genes associated with osteoclast differentiation, enhanced osteoclast number, and bone matrix degradation. In addition, the RANKL/OPG ratio was increased by ATRA, release of (45)Ca stimulated by ATRA was blocked by exogenous OPG, and mRNA expression of genes associated with bone formation was decreased by ATRA. All retinoid acid receptors (RARα/β/γ) were expressed in calvarial bones. Agonists with affinity to all receptor subtypes or specifically to RARα enhanced the release of (45)Ca and mRNA expression of Rankl, whereas agonists with affinity to RARβ/γ or RARγ had no effects. Stimulation of Rankl mRNA by ATRA was competitively inhibited by the RARα antagonist GR110. Exposure of calvarial bones to GC inhibited the stimulatory effects of ATRA on (45)Ca release and Rankl mRNA and protein expression. This inhibitory effect was reversed by the glucocorticoid receptor (GR) antagonist RU 486. Increased Rankl mRNA stimulated by ATRA was also blocked by GC in calvarial bones from mice with a GR mutation that blocks dimerization (GR(dim) mice). The data suggest that ATRA enhances periosteal bone resorption by increasing the RANKL/OPG ratio via RARα receptors, a response that can be inhibited by monomeric GR. Topics: Animals; Animals, Newborn; Bone Resorption; Mice; Osteoprotegerin; Periosteum; RANK Ligand; Receptors, Glucocorticoid; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Retinoids; Tretinoin | 2011 |
Decreases in bone mineral content by dietary all-trans retinoic acid precede decreases in bone mineral density in a weanling rat model of cigarette smoke-induced lung injuries.
Research has indicated that excessive vitamin A can have deleterious impacts on bone. Retinoic acid (RA), the most active metabolite of vitamin A, has been tested in clinical trials for treatment of lung cancer and emphysema. These trials are not measuring Bone Mineral Content (BMC) or Bone Mineral Density (BMD). In this study, we used an animal model to determine potential deleterious effects of all-trans RA on bone mass when used as a means to protect against or treat cigarette smoke-induced lung injuries, and also to evaluate BMC as a potential early indicator of osteoporosis risk. Twenty-four male weanling rats were fed either a control diet or a RA-supplemented diet. Half of each group was exposed to 40 cigarettes per day, 5 days per week, for 4 weeks. BMC and BMD were measured at weeks 2 and 4. RA supplementation in all groups significantly decreased (p < 0.05) only BMC at week 2 and both BMC and BMD (both p < 0.05) at week 4. The same results were observed when BMC was expressed relative to body weight. These data suggest that caution should be used when RA is used to treat smoke-related lung injuries. Topics: Absorptiometry, Photon; Animals; Atmosphere Exposure Chambers; Biomarkers; Bone Density; Bone Resorption; Dietary Supplements; Early Diagnosis; Lung Diseases; Male; Osteoporosis; Pulmonary Emphysema; Random Allocation; Rats; Rats, Sprague-Dawley; Smoking; Time Factors; Tretinoin; Weaning; Weight Gain | 2011 |
Oral treatment with retinoic acid decreases bone mass in rats.
13-cis-retinoic acid (13-cis-RA, isotretinoin) is used to treat severe recalcitrant acne. Other retinoids have adverse effects on bone. Recent studies of human patients treated with 13-cis-RA have had varying results, perhaps because of variability among patients and the lack of control groups. The effects of retinoids have been studied in rodents, but little information is available regarding the effects of clinically relevant retinoid doses as evaluated by use of bone densitometric techniques. We treated rats for 15 or 20 wk with 13-cis-RA, all-trans-RA, or soybean oil (control) by gavage. We used dual-energy X-ray absorptiometry, histomorphometry, and histologic evaluation to evaluate effects on bone. Spontaneous long bone fractures occurred in some rats treated with 15 mg/kg all-trans-RA daily. Bone mineral density, bone mineral content, bone diameter, and cortical thickness of the femur were reduced in rats treated daily with 10 or 15 mg/kg all-trans-RA or 30 mg/kg 13-cis-RA. The lumbar spine was not affected. Although the effects of 13-cis-RA were not as dramatic as those of all-trans-RA, further study of the effects of 13-cis-RA on long bones is warranted. Topics: Absorptiometry, Photon; Administration, Oral; Animals; Bone Density; Bone Resorption; Dermatologic Agents; Disease Models, Animal; Female; Humans; Isotretinoin; Male; Osteoporosis; Rats; Rats, Sprague-Dawley; Species Specificity; Tretinoin | 2006 |
Bone resorption activity of all-trans retinoic acid is independent of vitamin D in rats.
The mechanism by which all-trans retinoic acid (ATRA) induces bone resorption is unknown. However, an interaction between vitamin A and vitamin D has been established. In fact, although the mechanism is still unclear, vitamin A has been shown to be a weak antagonist of the actions of vitamin D. Taking into account this interaction and the influence of vitamin D on other calcitropic hormones, such as parathyroid hormone, the effect of vitamin D on ATRA-induced bone resorption was investigated. Vitamin D-deficient rats were fed diets containing 0 or 150 micro g of ATRA/g of diet. The rats then were orally administered 0 or 625 ng of cholecalciferol (vitamin D(3)) daily. Various bone parameters were measured after 3-8 wk. Regardless of the presence or absence of vitamin D(3), ATRA was able to cause bone resorption. In addition to examining the effect of vitamin D on ATRA-induced bone resorption under normal conditions, this effect also was studied under conditions that inhibit bone mineralization or growth by altering dietary calcium (Ca) and phosphorus (P) levels. Changes in dietary levels of Ca and P did not affect the ability of ATRA to cause bone resorption. Interestingly, despite its ability to stimulate bone resorption, ATRA did not affect serum calcium or phosphorus levels. Overall, the ability of ATRA to cause bone resorption is not dependent on vitamin D(3), dietary Ca or dietary P. Topics: Animals; Bone Density; Bone Development; Bone Resorption; Calcium; Calcium, Dietary; Cholecalciferol; Dose-Response Relationship, Drug; Male; Phosphorus; Phosphorus, Dietary; Rats; Tretinoin; Vitamin D Deficiency | 2003 |
Differential effects of glucocorticoids on bone resorption in neonatal mouse calvariae stimulated by peptide and steroid-like hormones.
Differential effects on in vitro bone resorption were observed when the glucocorticoids, hydrocortisone and dexamethasone, were added to neonatal mouse calvariae treated with either parathyroid hormone (PTH), 1,25(OH)2-vitamin D3, all trans-retinoic acid (t-RA), or prostaglandin E2 (PGE2). Bone resorption was assessed by analyzing either the release of 45Ca from [45Ca]CaCl2 prelabeled calvarial bones or the release of 3H from [3H]proline prelabeled calvariae. At PGE2 concentrations of 3 x 10(-8) and 3 x 10(-7) mol/l, co-treatment with either 10(-6) mol/l dexamethasone or 10(-6) mol/l hydrocortisone caused additive 45Ca release from neonatal mouse calvariae. In contrast, synergistic release from mouse calvarial bones of both 45Ca and 3H was found after either 10(-6) mol/l hydrocortisone or 10(-6) mol/l dexamethasone was combined with 3 x 10(-11) mol/l PTH treatment for 120 h. Dose-response studies indicated that the synergistic stimulation of 45Ca release from neonatal mouse calvariae by glucocorticoids and PTH could be elicited at glucocorticoid concentrations of 10(-8) to 10(-6) mol/l and at PTH concentrations of 10(-11) to 10(-9) mol/l. Progesterone and RU 38486 (a derivative of 19-nortestosterone with antiglucocorticoid activity) blocked the synergism noted with glucocorticoid and PTH co-treatment, suggesting that interaction between the steroids and PTH was dependent on glucocorticoid receptor interaction. Addition of either 10(-6) mol/l hydrocortisone or 10(-6) mol/l dexamethasone to neonatal mouse calvariae treated with 1,25(OH)2-vitamin D3 (10(-11) and 10(-10) mol/l) also resulted in synergistic stimulation of 45Ca release. In contrast to these observations, the stimulatory effect of t-RA (10(-8) mol/l) on 45Ca release from calvarial bones was abolished in the presence of 10(-6) mol/l dexamethasone. These results suggest that an important role of glucocorticoids may be to synergistically potentiate bone resorption stimulated by PTH and 1,25(OH)2-vitamin D3, but indicate an opposing interaction between the glucocorticoids and bone resorptive retinoids. Topics: Animals; Animals, Newborn; Bone Resorption; Calcitriol; Calcium; Culture Techniques; Dexamethasone; Dinoprostone; Drug Synergism; Glucocorticoids; Hydrocortisone; Mice; Mice, Inbred Strains; Parathyroid Hormone; Proline; Skull; Stimulation, Chemical; Tretinoin; Tritium | 1997 |
[Effect of kanggusong in prevention and treatment of retinoic acid induced osteoporosis in rats].
Retinoic acid 70 mg/kg.d was given by gastrogavage to Wistar rat for 14 days to induce osteoporosis. Kanggusong (KGS), a mixture of extracts from 8 traditional Chinese drugs, was given to 3 test groups of rats simultaneously in various dosage. Results showed that the KGS displayed obvious action in preventing osteoporosis, the trabecular loss of tibiae and bone loss of compact bone were lowered markedly in KGS groups with high (3.0 g/kg.d) or middle (1.0 g/kg.d) dosage in comparing with control model group, the trabecular area percentage and compact bone area percentage were increased significantly (P < 0.05) which approached to the level of normal control group. KGS could also improve the pathological changes in microstructure of bone, increase the thickness of trabecula and cortex (P < 0.05), reduce the trabecular gap and bone marrow cavity (P < 0.05). The mechanism of KGS might be relevant with its action of suppressing the osteoclast activity and activating osteoblast, resulting a positive balance of bone metabolism, increasing the blood concentration of calcium and estrogen as well as its antagonistic action against the injury of sex glands by retinoic acid. Topics: Animals; Bone Resorption; Drug Combinations; Drugs, Chinese Herbal; Male; Materia Medica; Osteoporosis; Ostreidae; Rats; Rats, Wistar; Tretinoin | 1996 |
Retinoic acid induces cell proliferation and modulates gelatinases activity in human osteoclast-like cell lines.
The effect of Retinoic Acid (RA) on human osteoclast-like cell lines, obtained from Giant Cell tumors (GCT) of bone, has been investigated evaluating its action on bone resorption, cell proliferation, microtubular organization and gelatinases expression and activity. Increasing concentrations of RA significantly dose-dependently decreased GCTs bone resorption, while 10(-7) M RA promoted an increase of cell proliferation. By immunofluorescence we demonstrated that GCTs express A and B gelatinases and, by zymography, that their activity was enhanced in medium collected from GCTs cultured in the presence of 10(-7) M RA. These data indicate that RA increases cell proliferation and modulates metalloproteinases (MMPs) activity, crucial events during the migration of osteoclast precursors toward bone surfaces. Topics: Bone Resorption; Cell Division; Fluorescent Antibody Technique; Gelatinases; Humans; Osteoclasts; Thymidine; Tretinoin; Tritium; Tumor Cells, Cultured | 1996 |
[A model of osteoporosis induced by retinoic acid in male Wistar rats].
An animal model of osteoporosis induced by retinoic acid was successfully established in 3-month-old male Wistar rats. The animals were given the drug 70 mg.kg-1.d-1 for 14 d intragastrically and sacrificed on day 29. The proximal tibia and middle tibia of the rats were processed undecalcifiedly for quantitative bone histomorphometry. Compared with the control rats, the cancellous and compact bone volume of the model rats were reduced markedly. The bone tissue microstructure showed some obvious pathological changes that the trabecular number were decreased, the separation of trabecular and medulla ossium cavity became large, the thickness of trabecular and cortex of bone were decreased. The mechanism of bone loss in the model rats was that the osteoclast was activated by retinoic acid which promoted bone resorption. Other changes in the model rats were also observed such as: the body weight, and the weights of seminal vesicle and prostate were decreased, the adrenal glands and spleen showed hyperplasia and hypertrophy. No change of the blood concentration of calcium, phosphorus, alkaline phosphatase, alanine transaminase, estradiol and testosterone in the model rats was observed. Topics: Animals; Bone Resorption; Disease Models, Animal; Male; Osteoporosis; Rats; Rats, Wistar; Tretinoin | 1996 |
Retinoic acid directly stimulates osteoclastic bone resorption and gene expression of cathepsin K/OC-2.
Vitamin A metabolites such as all-trans-retinoic acid (all-trans-RA) affect several steps of metabolic processes in vertebrates. In the last few years, several studies have shown the effect of RA on bone formation and metabolism. However, mechanisms of its action still remain unclear, especially with respect to the regulation of bone cells. Therefore, this study was carried out to clarify how RA regulates the activity of osteoclasts. Using a pit assay involving unfractionated bone cells, including osteoclasts obtained from rabbits, we found that RA stimulated an increase in the bone-resorbing activity in a dose- and time-dependent manner. Furthermore, this effect occurred more rapidly than that of treatments with 1 alpha,25-dihydroxyvitamin D3. However, this effect of RA may be partly related to cross-talk between osteoclasts and other types of cells. Therefore we studied the effect of RA on isolated osteoclasts. We found that all-trans-RA regulates the gene expression of cathepsin K/OC-2, a dominant cysteine proteinase, at the transcriptional level in mature osteoclasts isolated from rabbits. Moreover, retinoic acid-receptor alpha mRNA and retinoid X-receptor beta mRNA were expressed in these mature osteoclasts. Our results indicate that osteoclasts are target cells for RA and that RA might regulate a part of bone formation and metabolism through osteoclasts. Topics: Animals; Bone Resorption; Cathepsin K; Cathepsins; Cells, Cultured; Gene Expression Regulation, Enzymologic; Osteoclasts; Rabbits; Receptors, Retinoic Acid; Transcription, Genetic; Tretinoin | 1995 |
Retinoic acid induces osteoclast-like cell formation by directly acting on hemopoietic blast cells and stimulates osteopontin mRNA expression in isolated osteoclasts.
Although retinoic acid (RA) has been considered to be a bone-resorbing agent both in vivo and in vitro, its mechanism remains still unclear. The present study was performed to examine the effect of RA on osteoclast-like cell formation in the presence or absence of osteoblasts and to study whether RA would affect osteopontin mRNA expression in isolated rabbit osteoclasts. RA (10(-8) and 10(-6) M) significantly stimulated the formation of osteoclast-like cell in osteoblast-containing mouse bone cell cultures. Also, RA caused a stimulation of osteoclast-like cell formation from hemopoietic blast cells supported by granulocyte macrophage-colony stimulating factor (GM-CSF) in mouse spleen cell cultures. However, RA did not affect blast cell number in these cultures and significantly inhibited GM-CSF-stimulated proliferation of hemopoietic blast cells. On the other hand, RA stimulated the bone-resorbing activity of mature osteoclasts in mouse bone cell cultures. Moreover, RA caused a stimulation of osteopontin mRNA expression in isolated rabbit osteoclasts. The present study demonstrated for the first time that RA stimulated osteoclast-like cell formation, presumably through directly acting on the hemopoietic blast cells, and that RA stimulated osteopontin mRNA expression in isolated rabbit osteoclasts. Topics: Animals; Bone Resorption; Calcitriol; Cell Division; Cells, Cultured; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cells; Mice; Mice, Inbred ICR; Osteoclasts; Osteopontin; Phosphoproteins; Rabbits; RNA, Messenger; Sialoglycoproteins; Spleen; Tretinoin | 1995 |
Inhibitory effects of 9-cis and all-trans retinoic acid on 1,25(OH)2 vitamin D3-induced bone resorption.
The effects of retinoic acid (RA), and calcitriol are mediated by specific nuclear receptors (RARs and VDR, respectively). Induction of RAR and VDR responsive elements in target genes requires a cofactor, the retinoid-X-receptor (RXR), with its ligand 9-cis RA. We have previously demonstrated the expression of RARs and RXRs in osteoblasts, and herein investigated the effects of the retinoids all-trans RA and 9-cis RA alone and combined with calcitriol on bone resorption in vitro, measured by 45Ca-release from prelabeled neonatal mouse calvarial bones. All-trans RA and 9-cis RA were powerful stimulators of bone resorption and essentially equipotent. At threshold concentrations (1 nM) both 9-cis RA and at-RA markedly inhibited the resorption induced by calcitriol (1 pM). The findings are compatible with a physiological role for retinoids in bone metabolism. Topics: Animals; Bone and Bones; Bone Resorption; Calcitriol; Dose-Response Relationship, Drug; Mice; Tretinoin | 1995 |
Trypsinized osteoclast-like multinucleated cells formed in rat bone marrow cultures efficiently form resorption lacunae on dentine.
Rat bone marrow cultures containing 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] formed multinucleated cells (MNCs) that had many characteristics of osteoclasts. These MNCs, which have a tartrate-resistant acid phosphatase (TRAP) activity, could be classified into two morphological types: one type had smooth cellular margins (smooth-margined MNCs) and the other type had irregular spike-like margins (stellate MNCs). When bone marrow cells depleted of authentic osteoclasts were seeded and cultured on dentine slices, only low numbers of resorption lacunae could be detected. However, when preformed MNCs were detached by trypsinization and replated on dentine slices, numerous resorption lacunae were observed by scanning electron microscopy on these slices. Formation of lacunae occurred reproducibly during the five to ten days of culture. We also examined the effect of retinoic acid on TRAP-positive MNC formation in this bone marrow culture system. Although RA inhibited total TRAP-positive MNC formation, it increased the ratio of stellate MNCs to smooth-margined MNC, suggesting that RA may have the ability to regulate the formation of active osteoclasts. Topics: Animals; Bone Marrow; Bone Resorption; Calcitriol; Cells, Cultured; Dentin; Giant Cells; Male; Microscopy, Electron, Scanning; Osteoclasts; Rats; Rats, Inbred Strains; Tretinoin; Trypsin | 1992 |
Effect of retinoic acid on the resorptive activity of chick osteoclasts in vitro.
Mixed cell suspensions mechanically isolated from the long-bones of day 20 prehatch chicks were cultured for 24 h on bone and sperm whale dentine slices in the presence of 0, 10, 100, and 1000 nM retinoic acid (RA). Significant inhibitions in the numbers of discrete lacunae resorbed per dentine slice, and in the ratio of lacunae per tartrate-resistant acid phosphatase-positive multinuclear cell were observed with all concentrations of RA studied. Semi-automated, 3-dimensional analysis of 733 pits was performed on one series of experiments using a tandem scanning (confocal) microscope, interfaced to an image analyzing computer. The majority of lacunae were small and unilocular; the plan areas of 90% of control pits were below 500 microns 2. Small but statistically significant increases in lacunar areas, but not mean or maximum depths or volumes, were observed in the presence of 10 and 100 nM RA; however, these changes were much smaller than the magnitude of the decrease in pit numbers. Thus, the overall effect of RA in this system was inhibitory. Our findings contrast with the well known stimulatory action of retinoids on bone resorption both in vivo and in organ culture, but may parallel the inhibitory effects of prostaglandins observed in disaggregated osteoclast systems. Topics: Animals; Bone Resorption; Cells, Cultured; Chick Embryo; Osteoclasts; Tretinoin | 1992 |
Leukemia inhibitory factor/differentiation-stimulating factor (LIF/D-factor): regulation of its production and possible roles in bone metabolism.
Leukemia inhibitory factor/differentiation-stimulating factor (LIF/D-factor), expression of its mRNA, and possible roles in bone metabolism were studied in murine primary and clonal osteoblast-like cells. Local bone-resorbing factors such as IL-1, TNF alpha, and LPS strongly induced expression of LIF/D-factor mRNA in both clonal MC3T3-E1 cells and primary osteoblast-like cells. Neither parathyroid hormone nor 1 alpha,25-dihydroxyvitamin D3 stimulated expression of LIF/D-factor mRNA. LIF/D-factor per se did not stimulate expression of its own mRNA. Appreciable amounts of LIF/D-factor were detected in synovial fluids from rheumatoid arthritis (RA) patients but not in those with osteoarthritis (OA). Simultaneous treatment with LIF/D-factor, IL-1, and IL-6 at the concentrations found in synovial fluids from RA patients greatly enhanced bone resorption, though these cytokines did not stimulate bone resorption when separately applied. This suggests that LIF/D-factor produced by osteoblasts is in concert with other bone-resorbing cytokines such as IL-1 and IL-6 involved in the bone resorption seen in the joints of RA patients. LIF/D-factor specifically bound to MC3T3-E1 cells with an apparent dissociation constant of 161 pM and 1,100 binding sites/cell. LIF/D-factor dose-dependently suppressed incorporation of [3H]thymidine into MC3T3-E1 cells. In addition, it potentiated the alkaline phosphatase activity induced by retinoic acid, though LIF/D-factor alone had no effect on enzyme activity. These results suggest that LIF/D-factor is involved in not only osteoclastic bone resorption but also osteoblast differentiation in conjugation with other osteotropic factors. Topics: Acid Phosphatase; Animals; Arthritis, Rheumatoid; Bone and Bones; Bone Resorption; Cells, Cultured; Dose-Response Relationship, Drug; Female; Growth Inhibitors; Interleukin-1; Interleukin-6; Leukemia Inhibitory Factor; Lipopolysaccharides; Lymphokines; Mice; Mice, Inbred C57BL; Osteoarthritis; Osteoblasts; Pregnancy; RNA, Messenger; Synovial Fluid; Tretinoin; Tumor Necrosis Factor-alpha | 1992 |
Effects of retinoic acid on bone formation and resorption in cultured mouse calvaria.
1. The effects of retinoids on bone metabolism were examined in newborn mouse calvaria. 2. Incubation of calvaria with 0.01-1 microM retinoic acid for 4 days decreased their alkaline phosphatase (ALP) activity, mineral content and collagen content in a concentration-dependent fashion. 3. With treatment for 2 days, retinoic acid (1 microM) decreased the ALP activity and collagen content, but not the mineral content. 4. All these inhibitory effects were observed in calvaria from 0-day-old mice, but no inhibition of ALP activity was observed in calvaria from 14-day-old mice. 5. 1-Hydroxyethylidene-1,1-bisphosphonate (HEBP, 1 mM), which inhibits bone resorption, prevented the effect of retinoic acid (1 microM) on the bone mineral content, but not the effects on ALP and collagen (synthesized by osteoblasts). HEBP (1 mM) alone had no effect on the calvarial mineral and collagen contents. 6. These findings indicate that retinoic acid both stimulates bone resorption and inhibits osteoblastic activity by different mechanisms, and that stimulation of bone resorption by retinoic acid is inhibited by HEBP. Topics: Alkaline Phosphatase; Animals; Bone and Bones; Bone Development; Bone Resorption; Calcium; Female; Hydroxyproline; Mice; Mice, Inbred Strains; Organ Culture Techniques; Osteoblasts; Osteoclasts; Phosphorus; Pregnancy; Retinaldehyde; Tretinoin; Vitamin A | 1991 |
Bone-resorbing agents affect the production and distribution of procollagenase as well as the activity of collagenase in bone tissue.
The participation of collagenase in bone resorption has been investigated by assaying the procollagenase extracted from fetal mouse calvaria cultured under a variety of conditions, and by evaluating its ability to degrade bone collagen. Procollagenase was found in two separate pools, one requiring demineralization for its extraction, the other not. Culturing the bones with PTH, 1,25-dihydroxyvitamin D3, prostaglandin E2, interleukin-1, tumor necrosis factor-alpha, catabolin, retinoic acid, or endotoxin (but not with heparin) induced resorption, enhanced lysosomal enzyme release, and markedly increased the procollagenase content of the second pool. The PTH-induced increase in procollagenase was dose dependent and paralleled the extent of calcium loss and lysosomal enzyme release. The increase in procollagenase was found in bone, periosteum, and sutures, where its distribution was similar to that of nonmineralized collagen. The increase in procollagenase was abolished by cycloheximide, but not by indomethacin, hydroxyurea, glucocorticoids, acetazolamide, bisphosphonates, or calcitonin. Calcitonin and bisphosphonates almost completely inhibited the PTH-induced Ca loss and lysosomal enzyme release, but only partially inhibited the PTH-induced loss of collagen. The latter was, however, completely prevented by the collagenase inhibitor, CI-1. CI-1 also partially inhibited the PTH-induced Ca loss. Moreover, collagen degradation occurred in PTH-precultured calvaria (but not in noncultured controls) when incubated in a buffer under nonviable and nondemineralizing conditions. This degradation was inhibited by collagenase inhibitors, either CI-1 or the natural tissue inhibitor of metalloproteinases. This work thus indicates that the resorption of fetal bone explants proceeds along with an accumulation of procollagenase, primarily within their nonmineralized matrix. Moreover the results suggest that collagenase is likely to participate in the degradation of the nonmineralized collagen of the bone explants. Whether it also participates in the degradation of the collagen of the mineralized matrix remains to be elucidated. Topics: Acetazolamide; Animals; Bone and Bones; Bone Resorption; Calcitonin; Calcitriol; Cells, Cultured; Collagenases; Cycloheximide; Dinoprostone; Enzyme Precursors; Fetus; Heparin; Hydroxyurea; Interleukin-1; Kinetics; Mice; Microbial Collagenase; Organophosphonates; Osteoclasts; Parathyroid Hormone; Prostaglandins E; Recombinant Proteins; Tretinoin; Triamcinolone; Tumor Necrosis Factor-alpha | 1988 |
Effect of vitamin A on bone resorption: evidence for direct stimulation of isolated chicken osteoclasts by retinol and retinoic acid.
The effects of retinol (vitamin A) and retinoic acid on primary cultures of isolated chicken osteoclasts have been studied. The experiments were performed to establish the direct actions of these two agents on the organization of cytoskeletal structures, on the acid phosphatase contents, and on the bone resorption activities of these cells. The results showed that by treating the cultures with retinol or retinoic acid, from 10(-8) to 10(-5) M, there were dose-related responses of the osteoclasts. Adhesion to the substratum was stimulated by increasing the number of cells exhibiting the specialized dot-like adhesion structures, or podosomes, which represent the active part of the sealing zone. The treatments also induced rearrangement of the microtubular patterns with reversible depolymerization of microtubules. Acid phosphatase activity was significantly higher both in vitamin A-treated osteoclasts and in their media. When [3H]proline-labeled bone particles were added to the retinoid-treated osteoclasts, the release of [3H]proline was increased significantly compared to controls. These results suggest that the two vitamin A metabolites cause several modifications of the metabolic status of isolated osteoclasts that result in augmented rates of bone resorption. Topics: Acid Phosphatase; Animals; Bone Resorption; Cell Adhesion; Cells, Cultured; Chickens; Fluorescent Antibody Technique; Microtubules; Osteoclasts; Reference Values; Tretinoin; Tubulin; Vitamin A | 1988 |
Hormonal regulation of the production of collagenase and a collagenase inhibitor activity by rat osteogenic sarcoma cells.
Collagenases that specifically cleave native collagen at neutral pH have been implicated in the maintenance and turnover of connective tissue. In bone, the origin of neutral collagenase has remained equivocal, although recent studies have indicated that it is synthesized by the osteoblast. In the present work, regulation of secretion of neutral collagenase and a collagenase inhibitory activity was investigated using the osteoblastic tumor cell line UMR 106-01 and a variety of bone-resorbing agents. Under basal conditions, UMR 106-01 cells produced very low levels of collagenase but substantial amounts of the inhibitory activity. Exposure to PTH and, to a lesser extent, 1,25-dihydroxyvitamin D3, prostaglandin E2, retinoic acid, and epidermal growth factor stimulated the release of collagenase, an effect not seen with interleukin-1 or heparin. The stimulation of collagenase by PTH was dose dependent, with a half-maximal response occurring at 10(-8) M. Inclusion of isobutylmethylxanthine decreased the concentration of PTH required to produce half-maximal stimulation to 2 X 10(-10) M, indicating action via cAMP. With respect to the inhibitory activity, PTH and epidermal growth factor were the only agents, among those tested, able to enhance its production. Both hormones caused a 50-100% increase over control levels 72 h after hormone administration. There were notable differences in the time courses of production of collagenase and the inhibitor. After treatment with PTH, the enzyme reached maximal concentrations between 12-48 h, but declined to undetectable levels by 96 h. In contrast, the inhibitory activity was secreted in a linear fashion, with the highest concentrations achieved around 72-96 h. These results suggest a complex pattern of regulation of collagenase and inhibitor secretion by the osteoblastic cell, with the steady accumulation of inhibitor perhaps being responsible for the ultimate curtailment of enzyme activity. Topics: Animals; Bone Resorption; Calcitriol; Cell Line; Cyclic AMP; Dinoprostone; Epidermal Growth Factor; Female; Kinetics; Microbial Collagenase; Osteosarcoma; Parathyroid Hormone; Prostaglandins E; Rats; Tretinoin; Uterus | 1987 |
Suppression by cyclohexanetriones of retinoic acid-induced cartilage degradation in vitro and teratogenicity in vivo.
In cultured fetal rat bones, cyclohexanetriones that stimulate prostaglandin synthesis inhibited retinoic acid-induced cartilage degradation in a dose-dependent manner. The inhibition by the cyclohexanetrione Ro 31-0521 was reversible, indicating that the effect was not due to cytotoxicity. Excess retinoic acid is teratogenic in rats and adversely affects the normal differentiation of various morphogenetic systems, depending on the time of administration. The following retinoic acid-induced malformations were suppressed by Ro 31-0521: malformations of long bones and of apical phalanges induced on days 13 and 15 of gestation, respectively; spina bifida and tail malformations induced on day 11 of gestation and cleft palate induced on day 15 of gestation. However, cleft palate and other head malformations including exencephaly induced by retinoic acid on day 11 of gestation were not suppressed but even increased by Ro 31-0521. At a high dose, Ro 31-0521 given alone on day 11 of gestation was embryolethal and teratogenic but was not on the tested other days, indicating that the cyclohexanetrione at specific stages and doses also interfered with normal morphogenesis like retinoic acid. Assuming that stimulation of prostaglandin synthesis is the main biological effect of the cyclohexanetriones, our findings suggest that prostaglandins may be involved in mediating retinoid action. Topics: Abnormalities, Drug-Induced; Animals; Bone Resorption; Cartilage; Cleft Palate; Cyclohexanes; Cyclohexanones; Gestational Age; Limb Deformities, Congenital; Male; Organ Culture Techniques; Prostaglandins; Proteoglycans; Rats; Reproduction; Tretinoin | 1986 |
Inhibition of bone resorption in culture by (+)-catechin.
A pretreatment with (+)-catechin renders embryonic mouse calvaria in culture resistant to the action of bone resorbing agents, either parathyroid hormone (PTH), prostaglandin E2 or retinoic acid, and inhibits in a parallel way the enhanced excretion of N-acetyl-beta-glucosaminidase, a reference lysosomal enzyme, induced by these agents; it has, however, no effect on the small spontaneous leakage of lactate dehydrogenase from the explants. Moreover, the resorption induced in calvaria by a pretreatment with PTH or retinoic acid is inhibited by a further culture with catechin. This inhibition of bone resorption is discussed in relation with the collagen-stabilizing properties of (+)-catechin. Topics: Animals; Benzopyrans; Bone Resorption; Calcium; Catechin; Dinoprostone; Isoenzymes; L-Lactate Dehydrogenase; Mice; Organ Culture Techniques; Parathyroid Hormone; Prostaglandins E; Tretinoin | 1986 |
Effects of retinoic acid on rat bone.
The effects of retinoic acid on rat bones were investigated. Fifteen adult male Sprague-Dawley rats were given various oral doses of retinoic acid (0-20 mg/kg body weight/day, 5 days/wk) and were killed after various treatment periods (1-17 wk). Histological and microradiographic examination of the bones showed the presence of lesions, the development of which was dependent on the dose and the duration of treatment. These lesions were characterized by a dissolution of bone matrix, leaving only fibrils, by osteocytic osteolysis and by an increase in osteoclastic resorption. Topics: Animals; Bone and Bones; Bone Resorption; Dose-Response Relationship, Drug; Male; Radiography; Rats; Rats, Inbred Strains; Tibia; Tretinoin | 1984 |
Retinoic acid-induced cartilage resorption: induction of specific changes in protein synthesis and inhibition by tunicamycin.
The addition of retinoic acid to fetal rat bones in culture induces the release of proteoglycans followed by cartilage resorption. In this system retinoic acid markedly suppressed 3H-leucine and 3H-mannose incorporation into acid-precipitable macromolecules, and specifically changed the 3H-leucine incorporation pattern as revealed by gel electrophoresis. Tunicamycin, which selectively inhibits glycosylation of the asparagine residues in proteins, prevented the cartilage cell degradation in response to retinoic acid. Inhibitors of DNA synthesis did not affect the retinoic acid-induced changes indicating that cell division was not required for the cartilage degradation processes induced by retinoic acid. In consideration of our previous and present demonstrations that retinoic acid-induced cartilage resorption required RNA, protein, and glycoprotein synthesis and specifically changed the protein synthesis pattern, we suggest that retinoic acid may exert its action by altering gene expression. Topics: Animals; Bone Resorption; Cartilage; Depression, Chemical; Electrophoresis, Polyacrylamide Gel; Female; Fetus; Glucosamine; Pregnancy; Protein Biosynthesis; Proteins; Rats; Tretinoin; Tunicamycin | 1982 |
Structure-activity relationship of retinoids in fetal rat bone cultures.
The structure-activity relationship of 29 retinoids was investigated in fetal rat bone organ cultures. Retinoids induced the release of proteoglycan followed by cartilage tissue breakdown. In this study the loss of RNA was used as a parameter for cartilage resorption. During 6 days of incubation RNA decreased up to 80% in presence of active retinoids. Thus the ED40 was determined from dose-response curves of the various retinoids. The new compounds, called arotinoids, which contained the retinoic acid carbon skeleton in a fixed cisoid geometric conformation, were up to 200 times more active than all-trans-beta-retinoic acid. The most active compound contained a tetramethylated tetralin ring and a second aromatic ring in the side chain. Several lines of evidence indicated that the carboxylic acid end group was essential for the activity of retinoids in fetal bone cultures. The new, highly active retinoids described here might be an excellent tool to investigate whether the retinoid action is mediated by specific cellular retinoid binding proteins. Topics: Animals; Bone and Bones; Bone Resorption; Cartilage; Culture Techniques; Dose-Response Relationship, Drug; Rats; Structure-Activity Relationship; Tretinoin | 1981 |
Porphobilinogen-accumulation by a porphyrin auxotrophic strain of Bacillus subtilis.
The amount of porphobilinogen accumulated by a Bacillus subtilis hemC mutant strain is dependent on time and exogenic aminolevulinic acid addition. hemC mutant seems to be suitable for porphobilinogen production on a large scale. Topics: Amanitins; Bone and Bones; Bone Resorption; Cycloheximide; Dactinomycin; Deoxyadenosines; DNA; Organ Culture Techniques; Proteins; Proteoglycans; RNA; Transcription, Genetic; Tretinoin; Vitamin A | 1978 |
Inhibition of vitamin A action in rat bone cultures by inhibitors of RNA and protein synthesis.
Using explanted humeri of late fetal rats, retinoic acid induced a dose- and time-dependent regression of cartilage. The retinoic acid-induced release of proteoglycan into the medium was blocked by inhibitors of RNA and protein synthesis, suggesting its dependence upon continuous RNA and protein synthesis. Topics: Amanitins; Bone and Bones; Bone Resorption; Cycloheximide; Dactinomycin; Deoxyadenosines; DNA; Organ Culture Techniques; Proteins; Proteoglycans; RNA; Transcription, Genetic; Tretinoin; Vitamin A | 1978 |
Effect of aspirin administration on retinoic acid toxicity in mice.
Topics: Animals; Aspirin; Bone Resorption; Female; Lethal Dose 50; Male; Mice; Prostaglandins; Tretinoin; Vitamin A | 1977 |