transforming-growth-factor-beta and Vitamin-D-Deficiency

Hepatic fibrosis develops or progresses in 25 % of patients with autoimmune hepatitis despite corticosteroid therapy. Current management regimens lack reliable noninvasive methods to assess changes in hepatic fibrosis and interventions that disrupt fibrotic pathways. The goals of this review are to indicate promising noninvasive methods to monitor hepatic fibrosis in autoimmune hepatitis and identify anti-fibrotic interventions that warrant evaluation. Laboratory methods can differentiate cirrhosis from non-cirrhosis, but their accuracy in distinguishing changes in histological stage is uncertain. Radiological methods include transient elastography, acoustic radiation force impulse imaging, and magnetic resonance elastography. Methods based on ultrasonography are comparable in detecting advanced fibrosis and cirrhosis, but their performances may be compromised by hepatic inflammation and obesity. Magnetic resonance elastography has excellent performance parameters for all histological stages in diverse liver diseases, is uninfluenced by inflammatory activity or body habitus, has been superior to other radiological methods in nonalcoholic fatty liver disease, and may emerge as the preferred instrument to evaluate fibrosis in autoimmune hepatitis. Promising anti-fibrotic interventions are site- and organelle-specific agents, especially inhibitors of nicotinamide adenine dinucleotide phosphate oxidases, transforming growth factor beta, inducible nitric oxide synthase, lysyl oxidases, and C-C chemokine receptors types 2 and 5. Autoimmune hepatitis has a pro-fibrotic propensity, and noninvasive radiological methods, especially magnetic resonance elastography, and site- and organelle-specific interventions, especially selective antioxidants and inhibitors of collagen cross-linkage, may emerge to strengthen current management strategies.

Topics: Adrenal Cortex Hormones; Antioxidants; Apoptosis; CCR5 Receptor Antagonists; Cytokines; Elasticity Imaging Techniques; Extracellular Matrix; Hepatitis, Autoimmune; Humans; Inflammation; Liver Cirrhosis; Magnetic Resonance Imaging; NADPH Oxidases; Nitric Oxide Synthase Type II; Oxidative Stress; Protein-Lysine 6-Oxidase; Receptors, CCR2; Severity of Illness Index; Transforming Growth Factor beta; Vitamin D Deficiency

Vitamin D is the major regulator of calcium homeostasis and protects the organism from calcium deficiency via effects on the intestine, kidney, parathyroid gland, and bone. Disturbances in the vitamin D endocrine system (e.g., vitamin D-dependent rickets type I and type II), result in profound effects on the mineralization of bone. Recent studies with vitamin D receptor knockout mice also show effects on bone. It is questioned whether vitamin D has a direct effect on bone formation and mineralization. In rickets and particular vitamin D receptor knockout mice, calcium supplementation restores bone mineralization. However, the vitamin D receptor is present in osteoblasts, and vitamin D affects the expression of various genes in osteoblasts. This review focuses on the role of vitamin D in the control of osteoblast function and discusses the current knowledge of the direct effects of vitamin D on mineralization. Moreover, the role of vitamin D metabolism and the mechanism of action of vitamin D and interaction with other hormones and factors are discussed.

Topics: Alkaline Phosphatase; Animals; Apoptosis; Bone Morphogenetic Proteins; Calcifediol; Calcification, Physiologic; Calcitriol; Calcium-Binding Proteins; Cell Division; Cell Line; Cytochrome P-450 Enzyme System; Extracellular Matrix; Extracellular Matrix Proteins; Gene Expression Regulation; Humans; Insulin-Like Growth Factor I; Integrin-Binding Sialoprotein; Matrix Gla Protein; Mice; Mice, Knockout; Minerals; Osteoblasts; Osteocalcin; Osteoclasts; Osteonectin; Osteopontin; Osteoporosis; Plasminogen; Prostaglandins; Rats; Receptors, Calcitriol; Rickets; Sialoglycoproteins; Steroid Hydroxylases; Transforming Growth Factor beta; Vitamin D; Vitamin D Deficiency; Vitamin D3 24-Hydroxylase

Human bone contains an abundance of polypeptide growth factors. These growth factors stimulate the proliferation and activity of bone cells and can stimulate bone formation. Data from this laboratory and others suggest that bone growth factors may act to couple bone formation to resorption to maintain bone mass during remodeling. Research is underway to study these growth factors in bones and teeth, and their possible roles in both the pathogenesis and the treatments of osteoporosis and dental diseases.

Topics: Animals; Bone and Bones; Bone Remodeling; Dentin; Estrogens; Growth Disorders; Growth Substances; Humans; Odontoblasts; Odontogenesis; Osteoarthritis; Osteogenesis; Osteoporosis; Periodontal Diseases; Somatomedins; Tooth; Transforming Growth Factor beta; Vitamin D Deficiency

Topics: Adrenal Cortex Hormones; Asthma; CD4-Positive T-Lymphocytes; Cholecalciferol; Dendritic Cells; Gene Expression; Humans; Interferon-gamma; Interleukins; Monocytes; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vitamin D Deficiency

Multiple sclerosis (MS) patients were randomized, in a double blind design, and placed into either a vitamin D supplemented group or a placebo control group. As expected, serum 25-hydroxyvitamin D levels increased significantly following 6 month vitamin D supplementation (17+/-6 ng/ml at baseline to 28+/-8 ng/ml at 6 months). Vitamin D supplementation also significantly increased serum transforming growth factor (TGF)-beta 1 levels from 230+/-21 pg/ml at baseline to 295+/-40 pg/ml 6 months later. Placebo treatment had no effect on serum TGF-beta 1 levels. Tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-13 were not different following vitamin D supplementation. IL-2 mRNA levels decreased following vitamin D supplementation but the differences did not reach significance. Vitamin D supplementation of MS patients for 6 months was associated with increased vitamin D status and serum TGF-beta 1.

Topics: Cytokines; Female; Humans; Immune System; Immune Tolerance; Inflammation Mediators; Interferon-gamma; Interleukin-13; Interleukin-2; Male; Multiple Sclerosis; RNA, Messenger; Transforming Growth Factor beta; Transforming Growth Factor beta1; Treatment Outcome; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency

Vitamin D deficiency is common and linked to poor prognosis in pulmonary arterial hypertension (PAH). We investigated the differential effect of basal vitamin D levels in monocrotaline (MCT) induced PAH in normal and vitamin D deficient (VDD) rats. Rats were fed a VDD diet and exposed to filtered fluorescent light to deplete vitamin D. Normal rats were pretreated with vitamin D 100 IU/d and treated with vitamin D 100 and 200 IU/d, while VDD rats received vitamin D 100 IU/d. Vitamin D receptor (VDR) silencing was done in human umbilical vein endothelial cells (HUVECs) using VDR siRNA. Calcitriol (50 nM/mL) was added to human pulmonary artery smooth muscle cells (HPASMCs) and HUVECs before and after the exposure to TGF-β (10 ng/mL). Vitamin D 100 IU/d pretreatment in normal rats up-regulated the expression of eNOS and inhibited endothelial to mesenchymal transition significantly and maximally. Vitamin D 100 IU/d treatment in VDD rats was comparable to vitamin D 200 IU/d treated normal rats. These effects were significantly attenuated by L-NAME (20 mg/kg), a potent eNOS inhibitor. Exposure to TGF- β significantly reduced the expression of eNOS and increased the mesenchymal marker expression in normal and VDR-silenced HUVECs and HPASMCs, which were averted by treatment and maximally inhibited by pretreatment with calcitriol (50 nM). To conclude, this study provided novel evidence suggesting the beneficial role of higher basal vitamin D levels, which are inversely linked with PAH severity.

Topics: Animals; Calcitriol; Human Umbilical Vein Endothelial Cells; Humans; Hypertension, Pulmonary; Monocrotaline; Pulmonary Arterial Hypertension; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Signal Transduction; Transforming Growth Factor beta; Vitamin D; Vitamin D Deficiency; Vitamins

Renal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D-deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week 20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial-mesenchymal transition (EMT), and Tgf-β mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-β1 (TGF-β1)-mediated down-regulation of E-cadherin and inhibited TGF-β1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-β1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-β/Smad2/3-mediated EMT in middle-aged male mice.

Topics: Actins; Animals; Antigens, CD; Cadherins; Calcitriol; Cell Line; Cholecalciferol; Epithelial-Mesenchymal Transition; Female; Fibrosis; Humans; Kidney; Kidney Diseases; Kidney Tubules, Proximal; Male; Mice; Mice, Inbred ICR; Organ Size; Transforming Growth Factor beta; Vimentin; Vitamin D; Vitamin D Deficiency

Immunological mechanisms have been proposed to underlie the pathogenesis of recurrent spontaneous abortion (RSA). Vitamin D has a potent immunomodulatory effect, which may affect pregnancy outcome. The objective of this study was to investigate 25-hydroxyvitamin D [25(OH) D] concentration and vitamin D receptor (VDR) expression in the decidual tissues of RSA patients. Thirty women with RSA (RSA group) and thirty women undergoing elective abortion (control group) were recruited during 2016 from gynecology outpatient clinics. We measured 25(OH) D, interleukin (IL)-17, IL-23, transforming growth factor β (TGF-β), VDR and 1-α-hydroxylase (CYP27B1) in decidual tissues collected during the abortion procedure. In the RSA group, 25(OH) D and TGF-β were significantly decreased while IL-17 and IL-23 were significantly increased compared with the control group. VDR expression was significantly decreased in the RSA group compared with the control group. Logistic regression analysis showed a significant negative correlation between 25(OH) D in decidual tissues and RSA. These results indicated that vitamin D concentrations in the decidua are associated with inflammatory cytokine production, suggesting that vitamin D and VDR may play a role in the etiology of RSA.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Abortion, Habitual; Adult; Decidua; Female; Humans; Interleukin-17; Interleukin-23; Logistic Models; Pregnancy; Pregnancy Trimester, Third; Receptors, Calcitriol; Risk Factors; Statistics, Nonparametric; Transforming Growth Factor beta; Vitamin D; Vitamin D Deficiency; Young Adult

Disruption of the TGF-β pathway is associated with liver fibrosis and suppression of liver tumorigenesis, conditions associated with low Vitamin D (VD) levels. However, potential contributions of VD to liver tumor progression in the context of TGF-β signaling remain unexplored. Our analyses of VD deprivation (VDD) in in vivo models of liver tumor formation revealed striking three-fold increases in tumor burden in Smad3(+/-) mice, with a three-fold increase in TLR7 expression compared to controls. ChIP and transcriptional assays confirm Smad3 binding at two TLR7 promoter SBE sites. Molecular interactions between TGF-β pathway and VDD were validated clinically, where an absence of VD supplementation was associated with low TGF-β pathway member expression levels and β-catenin activation in fibrotic/cirrhotic human liver tissues. Subsequent supplementing VD led to restoration of TGF-β member expression with lower β-catenin levels. Bioinformatics analysis provides positive supportive correlation between somatic mutations for VD-related genes and the TGF-β pathway. We conclude that VDD promotes tumor growth in the context of Smad3 disruption, potentially through regulation of TLR7 expression and β-catenin activation. VD could therefore be a strong candidate for liver cancer prevention in the context of aberrant Smad3 signaling.

Topics: Animals; Humans; Liver Neoplasms, Experimental; Male; Membrane Glycoproteins; Mice; Mice, Transgenic; Signal Transduction; Smad3 Protein; Toll-Like Receptor 7; Transforming Growth Factor beta; Vitamin D; Vitamin D Deficiency; Wnt Proteins

Topics: Biomarkers; Humans; Leiomyoma; Transforming Growth Factor beta; Uterine Neoplasms; Vitamin D Deficiency

Regulatory T cells and IgE receptors (CD23 and CD21) on B cells were assessed in vitamin D deficient pregnant women. For this, 153 pregnant women were recruited from a government hospital and were categorized into three groups based on 25-hydroxyvitamin D3 (25(OH)D3) status. Regulatory T cell population (Treg cells) and CD23/CD21 expression on B cells were quantified by FACS ARIA II in maternal blood at third trimester; and the same parameters were evaluated in cord blood soon after delivery. In addition, TGF β and IL-10 were quantified in maternal and cord blood by using Milliplex kits. In a representative sample of eight women from each group (vitamin D sufficient, insufficient and deficient), placental tissues were processed for mRNA expressions of vitamin D receptor (VDR), retinoic acid receptor (RXR), vitamin D binding protein (VDBP) and vitamin D regulating enzymes. Of the 153 pregnant women, 18 were sufficient (≥30 ng/mL), 55 were insufficient (20-29 ng/mL) and 80 were deficient (≤19 ng/mL) for 25(OH)D3 status. The maternal blood Treg cell population (mean (%)± SE) was lower (p<0.05) in 25(OH)D3 deficient (0.2 ± 0.01) pregnant women compared to insufficient (0.34 ± 0.01) and sufficient (0.45 ± 0.02) pregnant women. Similarly, cord blood Treg cell population (mean (%)± SE) was also lower (p<0.05) in 25(OH)D3 deficient (0.63 ± 0.03) pregnant women when compared to insufficient (1.05 ± 0.04) and sufficient (1.75 ± 0.02) pregnant women. Mean (%) ± SE of B cells with CD23 and CD21 in maternal blood was higher (p<0.05) in 25(OH)D3 deficient pregnant women (0.35 ± 0.02; 1.65 ± 0.04) when compared to insufficient (0.22 ± 0.02; 0.55 ± 0.05) and sufficient (0.15 ± 0.02; 0.21 ± 0.01) pregnant women. Similarly, mean (%)± SE of B cell population with CD23 and CD21 in cord blood was also higher (p<0.05) in 25(OH)D3 deficient (0.41 ± 0.02; 1.2 ± 0.03) when compared to insufficient (0.32 ± 0.01; 0.6 ± 0.05) and sufficient (0.2 ± 0.01; 0.4 ± 0.02) pregnant women. Regulatory cytokines, TGF β and IL-10 were lower (p<0.05) in 25(OH)D3 insufficient and deficient subjects. In the placenta tissue of women with 25(OH)D3 deficiency, the regulatory T cell transcription factor FOXP3, vitamin D receptor (VDR) and retinoic acid receptor (RXR) expressions were downregulated. In contrast, CD23, CD21 and VDBP expressions were upregulated in 25(OH)D3 deficient and insufficient women. Vitamin D regulating enzymes (CYP24A1, CYP2R1 and CYP27B1) expression were also altered in women w

Topics: Adult; Female; Forkhead Transcription Factors; Gene Expression; Humans; Interleukin-10; Pregnancy; Pregnancy Complications; Receptors, Calcitriol; Receptors, Complement 3d; Receptors, IgE; RNA, Messenger; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Vitamin D; Vitamin D Deficiency

Regulatory T cells and IgE receptors (CD23 and CD21) on B cells were assessed in vitamin D deficient pregnant women. For this, 153 pregnant women were recruited from a government hospital and were categorized into three groups based on 25-hydroxyvitamin D3 (25(OH)D3) status. Regulatory T cell population (Treg cells) and CD23/CD21 expression on B cells were quantified by FACS ARIA II in maternal blood at third trimester; and the same parameters were evaluated in cord blood soon after delivery. In addition, TGF β and IL-10 were quantified in maternal and cord blood by using Milliplex kits. In a representative sample of eight women from each group (vitamin D sufficient, insufficient and deficient), placental tissues were processed for mRNA expressions of vitamin D receptor (VDR), retinoic acid receptor (RXR), vitamin D binding protein (VDBP) and vitamin D regulating enzymes. Of the 153 pregnant women, 18 were sufficient (≥30ng/mL), 55 were insufficient (20-29ng/mL) and 80 were deficient (≤19ng/mL) for 25(OH)D3 status. The maternal blood Treg cell population (mean (%)±SE) was lower (p<0.05) in 25(OH)D3 deficient (0.2±0.01) pregnant women compared to insufficient (0.34±0.01) and sufficient (0.45±0.02) pregnant women. Similarly, cord blood Treg cell population (mean (%)±SE) was also lower (p<0.05) in 25(OH)D3 deficient (0.63±0.03) pregnant women when compared to insufficient (1.05±0.04) and sufficient (1.75±0.02) pregnant women. Mean (%)±SE of B cells with CD23 and CD21 in maternal blood was higher (p<0.05) in 25(OH)D3 deficient pregnant women (0.35±0.02; 1.65±0.04) when compared to insufficient (0.22±0.02; 0.55±0.05) and sufficient (0.15±0.02; 0.21±0.01) pregnant women. Similarly, mean (%)±SE of B cell population with CD23 and CD21 in cord blood was also higher (p<0.05) in 25(OH)D3 deficient (0.41±0.02; 1.2±0.03) when compared to insufficient (0.32±0.01; 0.6±0.05) and sufficient (0.2±0.01; 0.4±0.02) pregnant women. Regulatory cytokines, TGF β and IL-10 were lower (p<0.05) in 25(OH)D3 insufficient and deficient subjects. In the placenta tissue of women with 25(OH)D3 deficiency, the regulatory T cell transcription factor FOXP3, vitamin D receptor (VDR) and retinoic acid receptor (RXR) expressions were downregulated. In contrast, CD23, CD21 and VDBP expressions were upregulated in 25(OH)D3 deficient and insufficient women. Vitamin D regulating enzymes (CYP24A1, CYP2R1 and CYP27B1) expression were also altered in women with 25(OH)D3 deficiency. The current study s

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Adult; Biomarkers; Blotting, Western; Cells, Cultured; Cholestanetriol 26-Monooxygenase; Cytochrome P450 Family 2; Cytokines; Female; Fetal Blood; Humans; Infant, Newborn; Interleukin-10; Pregnancy; Real-Time Polymerase Chain Reaction; Receptors, Calcitriol; Receptors, Complement 3d; Receptors, IgE; Retinoid X Receptors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamin D3 24-Hydroxylase; Vitamins; Young Adult

Despite a significant improvement in the management of chronic kidney disease (CKD), its incidence and prevalence has been increasing over the years. Progressive renal fibrosis is present in CKD and involves the participation of several cytokines, including Transforming growth factor-β1 (TGF-β1). Besides cardiovascular diseases and infections, several studies show that Vitamin D status has been considered as a non-traditional risk factor for the progression of CKD. Given the importance of vitamin D in the maintenance of essential physiological functions, we studied the events involved in the chronic kidney disease progression in rats submitted to ischemia/reperfusion injury under vitamin D deficiency (VDD).. Rats were randomized into four groups: Control; VDD; ischemia/reperfusion injury (IRI); and VDD+IRI. At the 62 day after sham or IRI surgery, we measured inulin clearance, biochemical variables and hemodynamic parameters. In kidney tissue, we performed immunoblotting to quantify expression of Klotho, TGF-β, and vitamin D receptor (VDR); gene expression to evaluate renin, angiotensinogen, and angiotensin-converting enzyme; and immunohistochemical staining for ED1 (macrophages), type IV collagen, fibronectin, vimentin, and α-smooth mucle actin. Histomorphometric studies were performed to evaluate fractional interstitial area.. IRI animals presented renal hypertrophy, increased levels of mean blood pressure and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of ED1 cells, increased expression of collagen IV, fibronectin, vimentin and α-actin, and reduced expression of Klotho protein were observed. VDD deficiency contributed to increased levels of plasma PTH as well as for important chronic tubulointerstitial changes (fibrosis, inflammatory infiltration, tubular dilation and atrophy), increased expression of TGF-β1 and decreased expression of VDR and Klotho protein observed in VDD+IRI animals.. Through inflammatory pathways and involvement of TGF-β1 growth factor, VDD could be considered as an aggravating factor for tubulointerstitial damage and fibrosis progression following acute kidney injury induced by ischemia/reperfusion.

Topics: Actins; Acute Kidney Injury; Angiotensinogen; Animals; Disease Progression; Fibronectins; Kidney; Male; Rats; Rats, Wistar; Receptors, Calcitriol; Renal Insufficiency, Chronic; Renin; Reperfusion Injury; Transforming Growth Factor beta; Transforming Growth Factor beta1; Vitamin D Deficiency

Topics: Female; Humans; Male; Transforming Growth Factor beta; Vitamin D Deficiency

Transforming growth factor-beta 1 (TGF-β1) contributes to tissue repair by promoting tissue fibrosis, and elevations have been reported in patients with bone marrow fibrosis. The aim of this study was to evaluate the relationship between TGF-β1 levels and vitamin D deficiency.. All patients presenting to the outpatient Endocrinology and Metabolic Diseases clinic between June and September of 2008 were approached, and consenting patients who were deemed suitable candidates were enrolled. Hematological parameters were measured, along with serum levels of total and ionized calcium, phosphorus, parathyroid hormone, iron, folic acid vitamin B12 levels, 25 OH vitamin D3 (25OHD(3)) and TGF-β1.. A total of 132 patients were included in the study. Patients were divided into 4 groups based on levels of 25OHD(3) [group 1 (<5 ng/ml), 20 patients; group 2 (5-15 ng/ml), 38 patients; group 3 (16-30 ng/ml); and group 4 (>30 ng/ml), 28 patients]. TGF-β1 levels were higher in patients in group 1 compared to the other groups. Transforming growth factor-beta levels correlated negatively with vitamin D3 and positively with leukocyte count, platelet count, of MCV and MCH. Multiple regression analyses revealed TGF-β1 levels to be associated with 25OHD(3) as well as with platelet count.. Results of this study are suggestive of the presence of a significant relationship between TGF-β and vitamin D deficiency. Increased TGF-β1 and platelet count may be an early indicator of bone marrow fibrosis in patients with vitamin D deficiency.

Topics: Adult; Cross-Sectional Studies; Female; Humans; Male; Transforming Growth Factor beta; Vitamin D Deficiency

We demonstrated previously that implants of bone matrix prepared from vitamin D-deficient (-D) rats were less osteoinductive and contained less extractable mitogenic activity compared with control implants prepared from vitamin D-replete (+D) rats and proposed that bone from -D rats is deficient in one or more specific growth factors. To test this hypothesis, bones from rats that were fed either +D or -D diets and kept in the dark for 8 wk were extracted and assayed for insulin-like growth factors I and II (IGF-I and IGF-II) and transforming growth factor beta (TGF-beta), the three most abundant growth factors in rat bone, and osteocalcin. Serum calcium, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] were determined at sacrifice. In -D rats, there were significant reductions in serum calcium, 25-hydroxyvitamin D3, and 1,25(OH)2D3 and skeletal TGF-beta but no differences in extractable skeletal protein, IGF-I, IGF-II, or osteocalcin compared with +D rats. To determine whether 1,25(OH)2D3 increased TGF-beta production by bone cells, we treated mouse calvaria for 6 days and mouse osteoblasts for 2 days with 10 nM 1,25(OH)2D3. Production of TGF-beta was increased almost 100% by 1,25(OH)2D3. We conclude that vitamin D deficiency reduces deposition of TGF-beta in rat bone and that diminished skeletal TGF-beta could contribute to the previously observed decrease in osteoinduction in implants from -D rat bone. The findings support the possibility that vitamin D and bone-derived TGF-beta are required for normal repair of the skeleton.

Topics: Animals; Bone and Bones; Bone Development; In Vitro Techniques; Mice; Osteoblasts; Osteocalcin; Rats; Somatomedins; Transforming Growth Factor beta; Vitamin D Deficiency