acid-phosphatase and Malocclusion

Increased subchondral trabecular bone turnover due to imbalanced bone-resorbing and bone-forming activities is a hallmark of osteoarthritis (OA). Wnt5a/Ror2 signaling, which can derive from bone marrow stromal cells (BMSCs), takes a role in modulating osteoblast and osteoclast formation. We showed previously that experimentally unilateral anterior crossbites (UACs) elicited OA-like lesions in mice temporomandibular joints (TMJs), displaying as subchondral trabecular bone loss. Herein, we tested the role of BMSC-derived Wnt5a/Ror2 signaling in regulating osteoclast precursor migration and differentiation in this process. The data confirmed the decreased bone mass, increased tartrate-resistant acid phosphatase (TRAP)-positive cell number, and enhanced osteoclast activity in TMJ subchondral trabecular bone of UAC-treated rats. Interestingly, the osteoblast activity in the tissue of TMJ subchondral trabecular bone of these UAC-treated rats was also enhanced, displaying as upregulated expressions of osteoblast markers and increased proliferation, migration, and differentiation capabilities of the locally isolated BMSCs. These BMSCs showed an increased CXCL12 protein expression level and upregulated messenger RNA expressions of Rankl, Wnt5a, and Ror2. Ex vivo data showed that their capacities of inducing migration and differentiation of osteoclast precursors were enhanced, and these enhanced capabilities were restrained after blocking their Ror2 signaling using small interfering RNA (siRNA) assays. Reducing Ror2 expression in the BMSC cell line by siRNA or blocking the downstream signalings with specific inhibitors also demonstrated a suppression of the capacity of the BMSC cell line to promote Wnt5a-dependent migration (including SP600125 and cyclosporine A) and differentiation (cyclosporine A only) of osteoclast precursors. These findings support the idea that Wnt5a/Ror2 signaling in TMJ subchondral BMSCs enhanced by UAC promoted BMSCs to increase Cxcl12 and Rankl expression, in which JNK and/or Ca(2+)/NFAT pathways were involved and therefore were engaged in enhancing the migration and differentiation of osteoclast precursors, leading to increased osteoclast activity and an overall TMJ subchondral trabecular bone loss in the UAC-treated rats.

Topics: Acid Phosphatase; Animals; Anthracenes; Bone Density; Bone Remodeling; Cell Differentiation; Cell Movement; Cell Proliferation; Chemokine CXCL12; Coculture Techniques; Cyclosporine; Enzyme Inhibitors; Female; Isoenzymes; Malocclusion; MAP Kinase Signaling System; Mesenchymal Stem Cells; NFATC Transcription Factors; Osteoblasts; Osteoclasts; Random Allocation; RANK Ligand; Rats; Rats, Sprague-Dawley; Receptor Tyrosine Kinase-like Orphan Receptors; Signal Transduction; Tartrate-Resistant Acid Phosphatase; Temporomandibular Joint; Wnt Proteins; Wnt-5a Protein

Occlusal alignment is known clinically to have a widespread influence on the stomatognathic system, including the temporomandibular joint and masticatory muscles. However, while occlusion is still an important determinant of most dental treatments, the exact effect of occlusal alignment is unclear because of a lack of conclusive scientific evidence. In this study, a malocclusion model system is used to examine the cellular and histologic alterations in the contralateral condyle of mice after a malocclusion was induced by a build-up of resin on the left maxillary molars. A significant decrease in the thickness of the condylar cartilage was found in the 1-week experimental group, together with increased apoptosis and decreased proliferation in the condylar head, which included cartilage and subchondral bone. Additionally, the number of TRAP-positive osteoclasts and MPO- and F4/80-positive inflammatory cells in the subchondral bone were significantly higher in the 1-week experimental group. Unbalanced malocclusion caused increased bone remodeling, as evidenced by increased osteoclastic activity and inflammatory responses (macrophages and neutrophils, respectively). However, these alterations in the 1-week experimental group were subsequently attenuated and restored almost to the baseline at 3 weeks after the induction of the malocclusion.

Topics: Acid Phosphatase; Animals; Disease Models, Animal; Imaging, Three-Dimensional; In Situ Nick-End Labeling; Isoenzymes; Ki-67 Antigen; Male; Malocclusion; Mandibular Condyle; Mice; Mice, Inbred C57BL; Peroxidase; Tartrate-Resistant Acid Phosphatase

To investigate the changes in condylar cartilage and subchondral bone of the temporomandibular joint (TMJ) in a mouse model of incisor malocclusion.. By bonding a single (single group) or a pair (pair group) of metal tube(s) to the left incisor(s), a crossbite-like relationship was created between left-side incisors in mice. The morphological changes in the TMJ condyles were examined by hematoxylin and eosin and toluidine blue staining. Indices of osteoclastic activity, including tartrate-resistant acid phosphatase (TRAP) staining and macrophage colony stimulating factor (M-CSF) were investigated by histochemistry or real-time polymerase chain reaction (PCR). The osteoblastic activity was indexed by osteocalcin expression. Expressions of semaphorin 4D and its receptor, Plexin-B1, were detected by real-time PCR. Two-way analysis of variance was used to assess the differences between groups.. One week and 3 weeks after bonding the metal tube(s), cartilage degradation and subchondral bone loss were evident histologically. Both indices of osteoclastic activity (TRAP and M-CSF) were significantly increased in cartilage and subchondral bone after bonding the metal tube(s). Osteocalcin expression in cartilage was significantly increased at week 3, while its expression in subchondral bone was significantly increased at week 1 but decreased at week 3. The semaphorin 4D expression in cartilage and subchondral bone was significantly decreased at week 1 but significantly increased at week 3. For Plexin-B1 expression, a significant increase was detected in subchondral bone at week 3.. Bonding a single or a pair of metal tube(s) to left incisor(s) is capable of inducing remodeling in the TMJ, which involved cartilage degradation and alteration of osteoclastic and osteoblastic activity.

Topics: Acid Phosphatase; Animals; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Bone Remodeling; Bone Resorption; Cartilage, Articular; Chondrocytes; Coloring Agents; Disease Models, Animal; Fluorescent Dyes; Incisor; Isoenzymes; Macrophage Colony-Stimulating Factor; Malocclusion; Mandibular Condyle; Mice; Mice, Inbred BALB C; Nerve Tissue Proteins; Osteoblasts; Osteocalcin; Osteoclasts; Receptors, Cell Surface; Semaphorins; Tartrate-Resistant Acid Phosphatase; Temporomandibular Joint

Excessive mechanical stress (MS) during hyperocclusion is known to result in disappearance of the alveolar hard line, enlargement of the periodontal ligament (PDL) space, and destruction of alveolar bone, leading to occlusal traumatism. We have recently reported that MS induces predominantly C-C chemokine ligand (CCL) 2 expression in PDL tissues, leading, via C-C chemokine receptor (CCR) 2, to MS-dependent osteoclastogenesis in alveolar bone. Thus, we hypothesize that ablation of the CCL2/CCR2 signaling pathway should suppress MS-induced osteoclastogenesis-associated chemokines and alleviate occlusal traumatism. We examined the effect of MS on chemokine expression and osteoclastogenesis using in vivo and in vitro hyperocclusion models with CCL2-deficient (CCL2((-/-))) and CCR2-deficient (CCR2((-/-))) mice. Compared with that in wild-type mice, expression of CCL3 in PDL cells and TRAP-positive cells in alveolar bone from CCL2((-/-)) and CCR2((-/-)) mice was up-regulated, even in the absence of MS. Furthermore, the expression of CCL3 and TRAP-positive cells was significantly increased after both 4 and 7 days of hyperocclusal MS loading in CCL2((-/-)) and CCR2((-/-)) mice. Hyperocclusion induced compensatory CCL3 expression and promoted osteoclastogenesis to counterbalance deficient CCL2/CCR2 signaling, suggesting that co-expression of CCL3 with CCL2 may precipitate synergistic, MS-dependent alveolar bone destruction during occlusal traumatism.. MS, mechanical stress; PDL, periodontal ligament; CCL2, CC chemokine ligand 2 (MCP-1; monocyte chemoattractant protein-1); CCR2, CC chemokine receptor 2; CCL3, CC chemokine ligand 3 (MIP-1α); CCL5, CC chemokine ligand 5 (RANTES).

Topics: Acid Phosphatase; Alveolar Bone Loss; Alveolar Process; Animals; Biomechanical Phenomena; Cell Culture Techniques; Chemokine CCL2; Chemokine CCL3; Chemokine CCL5; Dental Occlusion, Traumatic; Isoenzymes; Malocclusion; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoclasts; Periodontal Ligament; Receptors, CCR1; Receptors, CCR2; Signal Transduction; Stress, Mechanical; Tartrate-Resistant Acid Phosphatase; Time Factors; Up-Regulation

The objective was to examine the effects of a lateral functional shift of the rat mandible and the effects of a shift release on the condylar cartilage during the growth period. Fifty 5-week-old male Wistar rats were initially divided into three groups: shift, recovery, and control. At 5 weeks of age, each animal in the shift and recovery groups received an appliance designed to produce a lateral functional shift of the mandible to the left side. For the recovery group, the appliance was removed after 2 weeks. For the shift group, the appliance was used for 4 weeks. Total cartilage thickness, 5-bromo-2'-deoxyuridine-labeling index, and toluidine blue and tartrate-resistant acid phosphatase-positive cell number in the condylar cartilage at 1, 2, 3, and 4 weeks were compared with those in age-matched controls that had no appliances. In the shift group at 2 weeks, the cartilage thickness and labeling index increased in the central region on the contralateral side, whereas these decreased in the lateral region on the ipsilateral side. However, in the recovery group, 1 to 2 weeks after appliance removal, the cartilage thickness and labeling index in both investigated regions became similar to the control groups. These results emphasize the importance of early treatment to normalize occlusion and create appropriate conditions for normal occlusal development.

Topics: Acid Phosphatase; Animals; Antimetabolites; Biomarkers; Bromodeoxyuridine; Cell Count; Coloring Agents; Dental Occlusion; Growth Plate; Isoenzymes; Male; Malocclusion; Mandible; Mandibular Condyle; Rats; Rats, Wistar; Recovery of Function; Tartrate-Resistant Acid Phosphatase; Tolonium Chloride

Orthodontic movement of non-occluding teeth may result in undesirable apical root resorption. These teeth present with a histologically altered periodontium and are considered to be hypofunctional. The purpose of this study was to compare the amount of root resorption associated with a normal and a hypofunctional periodontium in rats during experimental tooth movement caused by heavy continuous force. The mandibular first molar was induced into a non-occluding condition in the hypofunctional periodontium group. Mesial orthodontic force was applied by means of 50-gram-force closed-coil springs for 15 days in both groups. The active root-resorption lacunae from histological sections, identified by tartrate-resistant acid phosphatase, were measured in terms of length, depth, and area. The results showed that the amount of root resorption was significantly greater in teeth with a hypofunctional periodontium than in those with a normal periodontium (p < 0.05). These results suggest that orthodontic movement of non-occluding teeth should be performed with caution.

Topics: Acid Phosphatase; Animals; Biomarkers; Isoenzymes; Male; Malocclusion; Molar; Orthodontic Wires; Periodontium; Rats; Rats, Sprague-Dawley; Root Resorption; Statistics, Nonparametric; Stress, Mechanical; Tartrate-Resistant Acid Phosphatase; Tooth Movement Techniques; Weight-Bearing

Ruffini nerve endings (mechanoreceptors) in the periodontal ligament (PDL) of mouse incisors were examined to elucidate whether experimentally-induced crossbites cause any changes or abnormalities in their morphology and distribution. Anterior guiding planes were attached to the mandibular incisors of 3-week-old C3H/HeSlc mice. At 3 days and 1, 2, 4, 6, and 8 weeks post-attachment of the appliance, the mice were sacrificed by perfusion fixation. Frozen sagittal cryostat sections of the decalcified maxillary incisors were processed for immunohistochemistry of protein gene product 9.5, followed by histochemical determination of tartrate-resistant acid phosphatase activity to reveal sites of alveolar bone resorption. Despite the absence of bone resorption within the lingual PDL of control mice, distinct resorption sites were seen in the respective regions of the experimental animals. Unlike the controls, many Ruffini endings showing vague and swollen contours, with unusually long and pedunculated micro-projections were observed in the affected lingual PDL of the incisors in the experimental animals with short-term anterior crossbite induction. Club-shaped nerve terminations with few, if any, micro-projections were observed in the lingual PDL of experimental animals with long-term induction, as well as in aged control mouse incisors. Differences in the distribution of Ruffini endings were also observed. These results indicate that changing the direction of the force applied to the PDL results in rapid and prolonged changes in the morphology of Ruffini-like mechanoreceptors.

Topics: Acid Phosphatase; Alveolar Bone Loss; Analysis of Variance; Animals; Biomarkers; Bite Force; Immunohistochemistry; Incisor; Isoenzymes; Malocclusion; Maxilla; Mechanoreceptors; Mice; Mice, Inbred C3H; Mice, Inbred Strains; Microscopy, Electron; Nerve Endings; Nerve Tissue Proteins; Osteoclasts; Periodontal Ligament; Tartrate-Resistant Acid Phosphatase; Thiolester Hydrolases; Ubiquitin Thiolesterase

The present study was conducted to investigate the influence of vertical occlusal discrepancies on condylar remodeling and the subsequent craniofacial growth in growing rats. Thirty 4-week-old male Wistar strain rats were used. A 1-mm-thick metal plate was bonded onto the occlusal surface of the maxillary molars to increase posterior dentoalveolar height. During the early phase of the experiment, the thickness of the proliferative and maturative/hypertrophic zones in the anterior and superior portions of the condyle was significantly smaller in the experimental group than in the controls. The number of TRAP-positive cells was significantly greater in the experimental group than in the controls. At the end of the experiment, decreased ramus height and a large gonial angle were found in the experimental group. Changes in the intra-articular environment associated with vertical occlusal discrepancies may influence condylar and craniofacial growth in growing individuals, although some adaptive response of the condyle may be induced if growth potential remains.

Topics: Acid Phosphatase; Animals; Biomarkers; Bone Remodeling; Dental Stress Analysis; Isoenzymes; Male; Malocclusion; Mandibular Condyle; Maxillofacial Development; Osteoclasts; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Vertical Dimension

The effect of chronic mandibular protrusion on the collagenolytic and phosphatase activity of several mandibular bone sites and the condylar cartilage was evaluated. Ninety-three male Sprague-Dawley rats were equally divided into two experimental and one control group. One experimental group wore a protrusive appliance for 2 weeks, the other for 4 weeks. All animals were killed at 59 days of age. Collagenolytic, alkaline and cid phosphatase activities were determined in the condylar cartilage, the subchondral bone and condylar neck, and in the gonial angle and coronoid process. In the cartilage and subchondral bone, the protrusive appliance caused a reduction in collagenolytic and alkaline phosphatase activity. In the condylar neck, it caused a large increase in collagenolytic activity and a decrease in alkaline phosphatase activity in both experimental groups. In the gonial angle and coronoid process, the appliance increased the collagenolytic activity only in the 2-week group. In the 4-week group, the alkaline phosphatase and collagenolytic activities were not different from the activities in those tissues in the control animals. Thus a protrusive appliance induced quantitative changes in enzyme activities in condylar cartilage and mandibular bone. The increase in collagenolytic activity (representing increased bone resorption) occurred typically in areas of muscle attachment and might have been the result of the neuromuscular changes induced by the protrusive appliance. The recovery to normal values of collagenolytic activity in the coronoid process and gonial angle of the 4-week group suggests that at these sites the muscles (and subperiosteal bone) might have adapted to their new biomechanical environment after the longer period of appliance wear.

Topics: Acid Phosphatase; Adaptation, Physiological; Alkaline Phosphatase; Animals; Bone and Bones; Bone Resorption; Cartilage; Collagen; Male; Malocclusion; Mandibular Condyle; Rats; Rats, Inbred Strains

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Alveolar Process; Bone Resorption; Calcium; Child; Glucuronidase; Humans; Male; Malocclusion; Osteogenesis

Topics: Acid Phosphatase; Animals; Collagen; Fibroblasts; Lathyrism; Malocclusion; Periodontal Ligament; Rats