Objective. To investigate whether the reduction of discoidin domain receptor 2 (DDR-2), a cell membrane tyrosine kinase receptor for native type II collagen, attenuates the progression of articular cartilage degeneration in mouse models of osteoarthritis (OA).Methods. mice were subjected to microsurgical destabilization of the medial meniscus. Conditions of the articular cartilage from the knee joints of the double-heterozygous mutant and surgically treated mice were examined by histology, evaluated using a modified Mankin scoring system, and characterized by immunohistochemistry.Results. The rate of progressive degeneration in knee joints was dramatically reduced in the doubleheterozygous mutant mice compared with that in the type XI collagen-deficient mice. The progression in the double-heterozygous mutant mice was delayed by ϳ6 months. Following surgical destabilization of the medial meniscus, the progressive degeneration toward OA was dramatically delayed in the Ddr2 ؉/-mice compared with that in their wild-type littermates. The articular cartilage damage present in the knee joints of the mice was directly correlated with the expression profiles of DDR-2 and matrix metalloproteinase 13.Conclusion. Reduction of DDR-2 expression attenuates the articular cartilage degeneration of knee joints induced either by type XI collagen deficiency or by surgical destabilization of the medial meniscus.

Summary Objective The objective of this study is to characterize mouse temporomandibular joint (TMJ) following partial discectomy, since there is no documentation of whether or not partial discectomy can induce early-onset osteoarthritis (OA) in mouse TMJ. Methods Partial discs of TMJ in mice were removed by microsurgery. Histology was performed to characterize articular cartilages from the TMJ of mice. The morphology of the articular cartilages was evaluated using a modified Mankin scoring system. Immunohistostaining was carried out to examine the expression of discoidin domain receptor 2 (Ddr2), a type II collagen receptor, matrix metalloproteinase 13 (Mmp-13), and Mmp-derived type II collagen fragments in the articular cartilage of condyles from the mouse TMJ. Results Articular cartilage degeneration was seen in the mouse TMJ post discectomy, including increased proteoglycan staining in the extracellular matrix at 4 weeks, the appearance of chondrocyte clusters at 8 weeks, reduced proteoglycan staining and fibrillation at 12 weeks and the loss of articular cartilage at 16 weeks. Increased immunostaining for Ddr2, Mmp-13, and Mmp-derived type II collagen fragments was detected. Conclusion Results indicate that partial discectomy induces early-onset OA in mouse TMJ and that increased expression of Mmp-13, likely due to the elevated expression of Ddr2, may be one of the factors responsible for the early-onset OA in mouse TMJ.

Increased expression of the discoidin domain receptor 2 (DDR2) results from its interaction with collagen type II. This induces expression of matrix metalloproteinase (MMP)-13, leading to osteoarthritis (OA). To investigate the impact of the pericellular matrix of chondrocytes on DDR2, we generated a mouse model with inducible overexpression of DDR2 in cartilage. Conditional overexpression of DDR2 in mature mouse articular cartilage was controlled via the cartilage oligomeric matrix protein promoter using the Tet-Off-inducible system. Doxycycline was withdrawn at 1 month of age, and knee joints were examined at 2, 3, and 4 months of age. Microsurgery was performed on 3-month-old transgenic mice overexpressing DDR2 to destabilize the medial meniscus, and serial paraffin sections were examined at 2, 4, 8, and 12 weeks after surgery. DDR2 expression increased in the knee joints of transgenic mice. However, the increased DDR2 did not induce MMP-13 expression. No OA-like changes were observed in the transgenic mice at the age of 4 months. When transgenic mice were subjected to destabilizing of the medial meniscus, we observed accelerated progression to OA, which was associated with DDR2 activation. Therefore, conditionally overexpressing DDR2 in the mature articular cartilage of mouse knee joints requires activation to induce OA, and altered biomechanical stress can accelerate the onset of cartilage loss and progression to OA in transgenic mice.

Summary Objective The objective was to characterize the contralateral non-surgical temporomandibular joint (TMJ) in mice that had an opposing osteoarthrosis(OA)-like joint induced by unilateral partial discectomy. Methods TMJs on one side in mice were subjected to partial discectomy. Both surgical and contralateral non-surgical TMJs were collected at 4, 8, 12 and 16 weeks post-surgery for histological examination. The morphology of the articular cartilage of the condyle was evaluated using a scoring system. Results A progression of articular cartilage degeneration was seen in the TMJs following unilateral partial discectomy, including increased proteoglycan staining in the extracellular matrix at 4 weeks, the appearance of chondrocyte clusters at 8 weeks, reduced proteoglycan staining and fibrillation at 12 weeks and the loss of articular cartilage at 16 weeks. In the contralateral non-surgical TMJs, increased proteoglycan staining occurred in the articular cartilage of the condyle at 8 weeks and continued to age. Conclusion The result indicated that OA-like changes in one TMJ by partial discectomy could initiate early onset articular cartilage degeneration in the contralateral non-surgical TMJ in mice.

Summary Objective To determine whether reduction of the discoidin domain receptor 2 (Ddr2) delays the progression of condylar cartilage degeneration in the temporomandibular joint (TMJ) of mouse models with osteoarthritis (OA). Methods Double-heterozygous (Col11a1- and Ddr2-haploinsufficiency, Col11a1+/−;Ddr2+/−) mice were generated. TMJs of Ddr2+/− mice were subjected to partial discectomy. Condylar cartilage from the TMJ of Col11a1+/−;Ddr2+/− mice, surgically treated (discectomy) Ddr2+/− mice and their corresponding controls was characterized by means of histology and evaluated using a scoring system specific to mouse joints. Results The progression of condylar cartilage degeneration was significantly delayed in the TMJ of Col11a1+/−;Ddr2+/− mice compared with those of the Col11a1+/− mice. The progression of condylar cartilage degeneration in the TMJ of Ddr2+/− mice following discectomy was also significantly delayed when compared with their wild-type littermates. Conclusion Reduced expression of Ddr2 delays the progression of condylar cartilage degeneration, induced either by type XI collagen-haploinsufficiency or by a partial discectomy, in TMJ.