Calcitonin gene-related peptide enhances osteogenic differentiation and recruitment of bone marrow mesenchymal stem cells in rats.

The present study evaluated the effects of calcitonin gene-related peptide (CGRP) on bone marrow mesenchymal stem cells (BMMSCs) in vitro and in a rat model of mandibular distraction osteogenesis (MDO). Rat BMMSCs were isolated then treated with CGRP or CGRP antagonist (CGRP8-37). The proliferation and migration ability of BMMSCs was determined using 5-bromo-2'-deoxyuridine and Transwell assays, respectively. Osteogenic-related gene expression was analyzed with reverse transcription-quantitative polymerase chain reaction. For the in vivo analysis, thirty MDO rats were randomly assigned to control, CGRP or CGRP8-37 groups. To evaluate the mobilization of BMMSCs, nestin and stromal cell-derived factor 1 (SDF-1) were detected by immunohistochemistry and ELISA. Rats were sacrificed following 14 days and new bone formation was assessed by histological and micro-computed tomography analysis. In the in vitro results, the CGRP group demonstrated significantly higher migration and proliferation, as well as enhanced alkaline phosphatase and runt-related transcription factor 2 expression compared with the control. In the in vivo experiments, bone mineral density of the newly formed bone in the CGRP group was significantly higher than controls. The nestin and SDF-1 expression in the CGRP group was also significantly upregulated. In conclusion, the present study demonstrated that CGRP administration increased new bone formation, possibly via enhancing BMMSC migration and differentiation in MDO rats.

Relationship of distraction rate with inferior alveolar nerve degeneration-regeneration shift.

Distraction osteogenesis is an important technique for the treatment of maxillofacial abnormities and defects. However, distraction osteogenesis may cause the injury of the inferior alveolar nerve. The relationship between distraction rate and nerve degeneration-regeneration shift remains poorly understood. In this study, 24 rabbits were randomly divided into four groups. To establish the rabbit mandibular distraction osteogenesis model, the mandibles of rabbits in distraction osteogenesis groups were subjected to continuous osteogenesis distraction at a rate of 1.0, 1.5 and 2.0 mm/d, respectively, by controlling rounds of screwing each day in the distractors. In the sham group, mandible osteotomy was performed without distraction. Pin-prick test with a 10 g blunt pin on the labium, histological and histomorphometric analyses with methylene blue staining, Bodian's silver staining, transmission electron microscopy and myelinated fiber density of inferior alveolar nerve cross-sections were performed to assess inferior alveolar nerve conditions. At 28 days after model establishment, in the pin-prick test, the inferior alveolar nerve showed no response in the labium to a pin pricks in the 2 mm/d group, indicating a severe dysfunction. Histological and histomorphometric analyses indicated that the inferior alveolar nerve suffered more degeneration and injuries at a high distraction rate (2 mm/d). Importantly, the nerve regeneration, indicated by newborn Schwann cells and axons, was more abundant in 1.0 and 1.5 mm/d groups than in 2.0 mm/d group. We concluded that the distraction rate was strongly associated with the inferior alveolar nerve function, and the distraction rates of 1.0 and 1.5 mm/d had regenerative effects on the inferior alveolar nerve. This study provides an experimental basis for the relationship between distraction rate and nerve degeneration-regeneration shift during distraction osteogenesis, and may facilitate reducing nerve complications during distraction osteogenesis.

Preventing Early-Stage Graft Bone Resorption by Simultaneous Innervation: Innervated Iliac Bone Flap for Mandibular Reconstruction.

BACKGROUND: Postoperative resorption of vascularized bone grafts jeopardizes the success of dental implant(s) and functional rehabilitation of the jaw. Recent evidence supports the crucial role of innervation in bone regeneration and turnover. METHODS: This study reports a new technique for simultaneous innervation of vascularized iliac flaps in mandibular reconstruction, through neurorrhaphy between ilioinguinal nerves, which innervate iliac bone, and inferior alveolar nerves or great auricular nerves. Twenty-two patients (aged 50 to 69 years) with postoncologic continuity defects of the mandible underwent mandibular reconstruction (10 innervated flaps and 12 control flaps). Graft bone resorption was analyzed by computed tomographic scans at 6 and 12 months postoperatively, and bone quality was evaluated for dental implantation, with histologic and histomorphometric analyses for graft samples. RESULTS: At 12-month follow-up, graft bone density loss in the control group was significantly higher than in the innervated group (p < 0.05). Bone quality evaluation indicated a suitable condition for dental implantation in all patients in the innervated group but in 41.7 percent of patients in the control group. Histologic and histomorphometric analyses showed successful innervation in the innervated group but not in the control group. Osteoclast activity was significantly higher in the control group than in the innervated group (p < 0.05). CONCLUSIONS: Innervated iliac flaps may effectively prevent bone resorption of grafts in mandible reconstruction that otherwise jeopardize the success of dental implants. This new strategy of innervation of bone flaps appears clinically valuable and provides insights into the homeostasis of grafts for functional reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

CKIP-1 silencing promotes new bone formation in rat mandibular distraction osteogenesis.

OBJECTIVE: This study investigated the effects and possible molecular mechanism of casein kinase-2 interacting protein-1 (CKIP-1) silencing on bone regeneration during rat mandibular distraction osteogenesis (DO). STUDY DESIGN: CKIP-1 silencing by chitosan/si-CKIP-1 was employed and analyzed both in rat mandibular DO models in vivo and in cultured rat mandible bone marrow stromal cells (BMSCs) in vitro. RESULTS: Gross observation, micro-computed tomography analysis, and hematoxylin and eosin (H&E) staining revealed that new bone formation in the distraction gap of the chitosan/si-CKIP-treated group was better compared with the chitosan/si-NC and phosphate buffered saline-treated groups in both quantity and quality. Proliferation assay, flow cytometry, and alizarin red staining indicated that CKIP-1 silencing significantly inhibited apoptosis, but promoted osteogenic differentiation of cultured BMSCs. Additionally, CKIP-1 silencing significantly promoted the expression of Wnt3 a, ß-catenin, and osteocalcin both in new bone formation of DO models in vivo and in the osteogenic differentiation process of BMSCs in vitro. CONCLUSIONS: Promotion of bone formation after CKIP-1 silencing in rat mandibular distraction osteogenesis appears to be mediated through the Wnt3 a/ß-catenin signaling pathway.

Targeting P38 Pathway Regulates Bony Formation via MSC Recruitment during Mandibular Distraction Osteogenesis in Rats.

Distraction osteogenesis (DO) is a widely used self-tissue engineering. However, complications and discomfort due to the long treatment period are still the bottleneck of DO. Novel strategies to accelerate bone formation in DO are still needed. P38 is capable of regulating the osteogenic differentiation of both mesenchymal stem cells (MSCs) and osteoblasts, which are crucial to bone regeneration. However, it is not clear whether targeting p38 could regulate bony formation in DO. The purpose of the current work was to investigate the effects of local application of either p38 agonist anisomycin or p38 inhibitor SB203580 in a rat model of DO. 30 adult rats were randomly divided into 3 groups: (A) rats injected with DMSO served as the control group; (B) rats injected with p38 agonist anisomycin; (C) rats injected with p38 inhibitor SB203580. All the rats were subjected to mandibular distraction and the injection was performed daily during this period. The distracted mandibles were harvested on days 15 and 30 after surgery and subjected to the following analysis. Micro-computed tomography and histological evaluation results showed that local application of p38 agonist anisomycin increased new bone formation in DO, whereas p38 inhibitor SB203580 decreased it. Immunohistochemical analysis suggested that anisomycin promoted MSC recruitment in the distraction gap. In conclusion, this study demonstrated that local application of p38 agonist anisomycin can increase new bone formation during DO. This study may lead to a novel cell-based strategy for the improvement of bone regeneration.

Local injection of substance P increases bony formation during mandibular distraction osteogenesis in rats.

Substance P is a neuropeptide that is distributed in those sensory nerve fibres that innervate the medullary tissues of bone. It is a potent accelerator of proliferation and differentiation of osteoblasts in vitro. However, its capacity for promoting repair of mandibular defects is not known. We have investigated the osteogenic effects of local injections of substance P during mandibular distraction osteogenesis in rats. Twenty Sprague-Dawley rats were randomly assigned to 2 groups (n = 10 in each): substance P 10(-7) mmol/l in normal saline 0.2ml was injected into the experimental group, and saline alone into the controls. The mandibular distraction rate was 0.2mm every 12hours for 10 days. Daily injections of substance P or saline were given during the distraction period. Regeneration of bone was assessed quantitatively on days 15 and 29 using microcomputed tomography (microCT), and histological analysis. The rate of bony union in the group treated with substance P was significantly higher than that in the saline alone group on day 29 (p=0.001) The microCT images and quantitation showed more callus and more mature cortical bone when substance P was given than with control. Histological examination showed that cartilaginous tissues had formed in the middle of the distraction gaps in both groups. Bony bridges were seen only in the substance P group at the final time point (day 29). Injection of substance P into the gap of a rat mandible during mandibular distraction improved formation of good-quality bone and accelerated bony union.

Recruitment of exogenous mesenchymal stem cells in mandibular distraction osteogenesis by the stromal cell-derived factor-1/chemokine receptor-4 pathway in rats.

Distraction osteogenesis is widely used in orthopaedic and craniofacial surgery. However, its exact mechanism is still poorly understood. The purpose of this study was to find out whether there is systemic recruitment of mesenchymal stem cells (MSC) to the neocallus in the distraction gap by the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis during osteogenesis. We examined the migration of MSC towards a gradient of SDF-1 in vitro. We also transplanted MSC labelled with green fluorescent protein (GFP) intravenously, with or without treatment with CXCR4-blocking antibody, into rats that had had unilateral mandibular distraction osteogenesis, and investigated the distribution of cells labelled with GFP in the soft callus after 24 h. We found that SDF-1 facilitated the migration potency of MSC both in vitro and in vivo, and this migration could be inhibited by AMD3100, an antagonist of CXCR4, and promoted by local infusion of exogenous SDF-1 into the distraction gap. This study provides a new insight into the molecular basis of how new bone is regenerated during distraction osteogenesis.

A comparison of stromal cell-derived factor-1 expression during distraction osteogenesis and bone fracture in the mandible.

Distraction osteogenesis (DO) has been a widely applied technique in orthopedics and craniofacial surgery. However, the exact molecular mechanism by which the mechanical stimulus is translated into biological signals is still poorly understood. In this study, we examined and compared the expression of stromal cell-derived factor-1 (SDF-1) during mandibular distraction osteogenesis and fracture in rats, respectively. Forty-eight male Sprague-Dawley rats were divided into 2 groups and received unilateral distraction osteogenesis and rigid internal fixation, respectively, after the osteotomy on the right mandible. The harvested mandibles were examined radiographically, histologically, and immunohistochemically. We found that the expression of SDF-1 was mainly detected in the osteoblasts and blood vessels, and there were more intensive expression of SDF-1 in DO zones than in bone fracture zones. The quantitative analysis by enzyme-linked immunosorbent assay showed that SDF-1 reached a greater peak and maintained a longer period of up-regulation in DO than in fracture healing (P < 0.05). These results suggest that the distraction procedure markedly promotes the high expression of SDF-1 which facilitates the induction of bone formation during DO.

Effects of sympathetic innervation loss on mandibular distraction osteogenesis.

Sympathetic nerve system has been proved to have important regulative effects to bone mass. However, the role of sympathetic nerve system in distraction osteogenesis (DO) is unclear. Here we show that the sympathetic nerve system plays an important role in mandibular DO. Thirty male Sprague-Dawley rats were divided into 2 groups at random. Right-side mandibular DO was performed on the 15 rats in control group (group A). Bilateral transection of cervical sympathetic trunk and right-side mandibular DO were performed on the 15 rats in the experimental group (group B). After operation, quantitative general observations, micro-computed tomography bone morphology analysis, and hematoxylin-eosin staining osseous tissue on new osteotylus in distraction gap were performed at consolidation time of 1, 14, and 28 days. SPSS 12.0 software package was used for statistical analysis. At 1 and 14 days of consolidation time, there was more continuous bone formation in the experimental group than that of the control group as determined by gross observation. Bone formation parameters including bone mineral density, bone volume-total volume ratio, bone trabeculae number as determined by micro-CT, and histological study of the test group were significantly higher than those of the control group (P < 0.05). No significant difference was noted between the 2 groups on consolidation time of 28 days. Our study suggested that the sympathetic innervation loss could improve mandibular DO and new bone formation, and the sympathetic nerve system might negatively regulate the process of DO.

Local injection of nerve growth factor via a hydrogel enhances bone formation during mandibular distraction osteogenesis.

OBJECTIVE: The objective of this study was to evaluate the effects of the injectable NGF-carrying collagen/nano-hydroxyapatite/alginate hydrogel on the bone formation in a rabbit mandibular distraction osteogenesis model. STUDY DESIGN: Thirty-five New Zealand white rabbits underwent bilateral madibular distraction osteogenesis at a rate of 0.75 mm/12 h for 6 days. The rabbits were divided into 4 groups: group 1 received injections of collagen/nano-hydroxyapatite/alginate hydrogel containing hNGFß; groups 2, 3, and 4 received injections of hNGFß, Col/nHA/Alg hydrogel, and saline, respectively. The injections were performed on both sides of the mandible at the end of the lengthening phase. All the animals were killed at a consolidation time of 14 days. RESULTS: No difference in regenerate bone dimensions was observed among the 4 groups. Bone mineral density, the maximum load, and the bone volume/total volume of the new bone in the distraction gap in group 1 was significantly greater (P < .05) than in the other 3 groups. CONCLUSIONS: Application of the Col/nHA/Alg hydrogel as an NGF delivery during the consolidation phase of distraction osteogenesis increased regeneration and new bone formation.

Treatment of malignant triton tumor in zygomatic region.

Malignant triton tumor (MTT) is extremely rare and supposed to be highly aggressive because of high propensity for local recurrence and metastasis. To date, only about 170 cases were reported in various body locations including trunks, maxillary sinus, neck, extremities, retroperitoneal, and so on. We present a case of MTT in the zygoma with good outcome. A 27-year-old male patient with progressive swelling and pain in the right zygoma was proved to have an MTT by biopsy. Radical resection accompanying postoperative radiotherapy was adopted, and then the soft and hard tissue defects were repaired by prosthesis. The patient recovered well and was satisfied with the facial contour. At 45-month follow-up, there was no recurrence or metastasis that occurred. According to literature review, one third of MTTs appeared in the head and neck regions and seem to have a better prognosis. Radical resection is the most important remedy, and adjuvant radiotherapy could be helpful. With early finding and effective treatments, satisfactory outcome could be achieved.

Surgical treatment of a giant neurofibroma.

Neurofibromatosis type 1, an autosomal dominant inherited disease, presents pathologic symptoms of multiple systems, including neurofibromatosis, skeletal dysplasia, café-au-lait spots in skins, and so on. A 45-year-old man with neurofibromatosis type 1 was reported in this article. The patient presented a giant neurofibroma in his head and neck, dysplasia of skull, facial bones and spinal columns, and multiple café-au-lait spots in systematic skins. Satisfactory curative effects were obtained in this case after tumor resection and prosthesis implantation.

Nerve growth factor injected systemically improves the recovery of the inferior alveolar nerve in a rabbit model of mandibular distraction osteogenesis.

Our aim was to find out if nerve growth factor (NGF) injected systemically could improve the recovery of the inferior alveolar nerve in a rabbit model of mandibular distraction osteogenesis. We used 48 New Zealand white rabbits that were treated with bilateral distraction osteogenesis at a rate of 0.5mm/12h for 10 days. Immediately postoperatively, NGF or sodium chloride 0.6 µg/day was injected intramuscularly for 20 days. At the end of distraction and after consolidation times of 1, 2, and 4 weeks, the inferior alveolar nerves were evaluated histologically and histomorphometrically. Histologically, at 2 and 4 weeks there was less myelin debris, and more regenerating axons were present, in the NGF than the control groups. The density of myelinated axons was significantly greater in groups with NGF than controls at 2 and 4 weeks (p<0.05). NGF given systemically can accelerate the recovery of the inferior alveolar nerve in rabbits after mandibular distraction osteogenesis, and is a promising treatment option for neurological complications of mandibular distraction osteogenesis.

Surgical resection of a huge cemento-ossifying fibroma in skull base by intraoral approach.

Cemento-ossifying fibroma, also known as ossifying fibroma, usually occurs in the mandible and less commonly in the maxilla. The huge example in the skull base is even rare. We present a case of a huge cemento-ossifying fibroma arising below the skull base of a 30-year-old woman patient. Radiologic investigations showed a giant, lobulated, heterogeneous calcified hard tissue mass, which is well circumscribed and is a mixture of radiolucent and radiopaque, situated at the rear of the right maxilla to the middle skull base. The tumor expands into the right maxillary sinus and the orbital cavity, fusing with the right maxilla at the maxillary tuberosity and blocking the bilateral choanas, which caused marked proptosis and blurred vision. The tumor was resected successfully by intraoral approach, and pathologic examination confirmed the lesion to be a cemento-ossifying fibroma. This case demonstrates that cemento-ossifying fibroma in the maxilla, not like in the mandible, may appear more aggressive because the extensive growth is unimpeded by anatomic obstacles and that the intraoral approach can be used to excise the tumor in the skull base.

Open reduction and rigid internal fixation of dislocated condylar fractures: a long-term follow-up of 25 patients.

OBJECTIVE: To evaluate the long-term results of open reduction and rigid internal fixation for treatment of dislocated condylar process fractures. METHODS: Twenty-five patients with dislocated condylar fracture who underwent open reduction and rigid internal fixation were followed up for an average of 4.5 years and evaluated on the basis of occlusion, temporomandibular joint (TMJ) function and radiographs. RESULTS: Clinically, both occlusion and TMJ function were satisfactory. Generally, the dislocated condyles were well repositioned into the glenoid fossa after rigid internal fixation and remained in the position during the follow-up on the radiographs. CONCLUSION: Open reduction and rigid internal fixation could achieve satisfactory results for the treatment of dislocated condylar fractures.

Tisssue responses in corticotomy- and osteotomy-assisted tooth movements in rats: histology and immunostaining.

INTRODUCTION: The purpose of this histologic study was to examine underlying cellular responses to corticotomy- and osteotomy-assisted tooth movements. METHODS: Thirty-six rats were divided into 5 groups: corticotomy-assisted tooth movement (CO + TM), sham corticotomy without tooth movement (CO alone), osteotomy-assisted tooth movement (OS + TM), sham osteotomy without tooth movement (OS alone), and unassisted tooth movement (TM alone). Standard orthodontic springs were activated to produce mesial tooth movement. The rats were killed at 3, 21, and 60 days after activation for osteoclast and blood vessel counts, and immunostaining with proliferating cell nuclear antigen (PCNA), transforming growth factor beta 1 (TGF beta 1), vascular endothelial growth factor (VEGF), and osteocalcin were performed. RESULTS: The CO + TM group had significantly more osteoclasts at 3 days (P <0.005) compared with the OS + TM group. The alveolar bone surrounding the dental roots was replaced with multicellular tissue at 21 days in the CO + TM group but was intact in the OS + TM group with the exception of a distal distraction site. At day 21, immunostaining with PCNA, TGF beta 1, VEGF, and osteocalcin occurred at the mesial border of bone in the CO + TM group, whereas a diffuse pattern was observed in the distal distraction sites at 21 and 60 days in the OS + TM group. CONCLUSIONS: Corticotomy-assisted tooth movement produced transient bone resorption around the dental roots under tension; this was replaced by fibrous tissue after 21 days and by bone after 60 days. Osteotomy-assisted tooth movement resembled distraction osteogenesis and did not pass through a stage of regional bone resorption.

Effects of nerve growth factor delivery via a gel to inferior alveolar nerve in mandibular distraction osteogenesis.

Inferior alveolar nerve (IAN) injury is a concern in mandible distraction osteogenesis (DO). We have previously demonstrated that repeated local injections of human nerve growth factor beta (NGF-beta) have significantly enhanced the histologic recovery of the IAN in a rabbit model of DO. This study was to further test the effect of a single injection of human NGF-beta delivered via a collagen/nanohydroxyapatite/kappa-carrageenan gel to the recovery of the IAN in DO. Rabbits underwent mandibular DO at a rate of 0.75 mm/12 h for 6 days. At the end of the distraction period, injections were performed near the IAN percutaneously as follows: group 1, human NGF-beta in the gel; group 2, human NGF-beta in saline; group 3, the gel alone; and group 4, saline alone. At 14 days after the end of distraction, IAN histologic findings and histomorphometric parameters were evaluated. Histologically, there were less myelin debris and more abundant regenerating nerve fibers in group 1 than the other groups. Both the myelinated fiber density and the myelinated axon area in group 1 were significantly higher than groups 3 and 4 (P < 0.01); the myelinated axon area in the group 1 was significantly higher than group 2 (P < 0.01). In conclusion, the delivery of human NGF-beta in the gel leads to a better acceleration of the IAN injury recovery over the saline delivery. It provides a possible way to enhance the recovery of nerve injuries in craniofacial DO clinically.

Dentists' role in treating facial injuries sustained in the 2008 earthquake in China: how dental professionals can contribute to emergency response.

BACKGROUND: A major earthquake struck Sichuan province, China, on May 12, 2008, and the authors were involved in the medical response to the disaster in Jiangyou City, an area hard-hit by the quake. In this article, they analyze data about the earthquake-related facial injuries and assess dentistry's role in treating them. METHODS: This descriptive study included review of medical records for 4,582 patients with earthquake-related trauma at eight hospitals in Jiangyou, a city severely affected by the earthquake, for the day of the disaster and the 14 days immediately afterward. RESULTS: Of the 4,582 patients, 408 (8.9 percent) sustained a total of 482 facial injuries. The dental team treated patients with facial injuries and others who needed care. CONCLUSIONS: Facial injuries constitute a significant portion of earthquake-related trauma, and dentists therefore are an important part of the medical team that deals with such trauma. Dentists are a reliable force in the medical response to earthquakes and other disasters. CLINICAL IMPLICATIONS: The dental team should play an important role in disaster response. Establishing oral and maxillofacial surgeon (OMS)/dentist reserves and active leagues that use OMSs' and general dentists' offices as bases can help improve disaster response.

The association between roofing material and head injuries during the 2008 Wenchuan earthquake in China.

STUDY OBJECTIVE: We analyze the spectrum of earthquake-related head injuries resulting in hospitalization and arising from the 2008 Wenchuan Earthquake in China. An additional objective is to assess injury patterns associated with 2 types of roofing structures found in this region of China. METHODS: This descriptive study included data on trauma patients at 8 hospitals in Jiangyou for the 14 days immediately after the earthquake. The patients were either from Jiangyou County, which experienced a modified Mercalli intensity level of VIII, or from Beichuan County (Mercalli intensity level of X). Of the 5,775 earthquake-related injuries, 1,484 (25.7%) involved the head and were classified into 4 categories. Seven injury mechanisms were also analyzed to determine the association with the 4 types of head injuries. RESULTS: Scalp injuries (43%) were the most common type of head injuries, followed by facial injuries, 482 (32%), intracranial injuries, 218 (15%), and skull fractures, 117 (8%). Differences in injury type and cause were apparent, with scalp injuries being more common (49%) in Jiangyou than in Beichuan (30%) and falling clay tiles contributing more (40%) to this injury in the former city than the latter (6%). In contrast, precast concrete plank roofing caused 20% of scalp injuries in Beichuan compared with 3% in Jiangyou. CONCLUSION: Scalp injuries were the most common head injury type. Falling clay roofing tiles and precast concrete plank roofs are important injury mechanisms, and their contribution may reflect differences in building construction.

Matrix metalloproteinase and its inhibitor in temporomandibular joint osteoarthrosis after indirect trauma in young goats.

Our aim was to examine the change in expression of matrix metalloproteinases (MMP-13), matrix metalloproteinases-3 (MMP-3), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the articular cartilage of goats with experimentally-induced osteoarthrosis of the temporomandibular joint (TMJ) at various times. Osteoarthrosis was induced in 20 goats in the bilateral TMJ and 5 goats acted as controls. There were 5 goats in each group, and a group was killed at 7 days, and 1, 3, and 6 months postoperatively. The samples were collected, and the joints evaluated histologically. Immunofluorescence was used to detect the presence of MMPs and TIMP-1 in the articular disc and condylar cartilage. The ultrastructure of the articular disc and condylar surface at 1 month was examined with scanning electron microscopy (SEM). Osteoarthrosis of the TMJ progressed gradually over time. MMP-13, MMP-3, and TIMP-1 were expressed strongly in the TMJ soon after injury; MMP-13 became gradually weakened, and MMP-3 strengthened later. None of these were expressed in the normal condyle. After a month the surface of the arthrotic condyle was uneven, and the underlying collagen fibrils were exposed in irregular fissures on the surface. The secretion of TIMP-1 was related closely to the changes of MMPs during osteoarthrosis of the TMJ. The unbalanced ratio between them caused degradation of the matrix of the cartilage and might be the cause of osteoarthrosis of the TMJ.