Mice Deficient in Biglycan and Fibromodulin as a Model for Temporomandibular Joint Osteoarthritis

Wadhwa, Sunil; Embree, Mildred C.; Ameye, Laurent; Young, Marian F.

doi:10.1159/000091375

Cited by 44 publications

(40 citation statements)

References 67 publications

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“…4). At 4 and 8 weeks, experimental condyles displayed classical histopathological features of osteoarthritis (3,21,22), including surface irregularities and fissures (black triangles), a multifocal decrease in cells (asterisks), and the formation of chondrocyte clusters (black arrows) (Fig. 4a, top and middle panels).…”

Section: Resultsmentioning

confidence: 99%

Soft tissue ossification and condylar cartilage degeneration following TMJ disc perforation in a rabbit pilot study

Embree

Iwaoka

Kong

et al. 2015

Osteoarthritis and Cartilage

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Objective There are limited clinical treatments for temporomandibular joint pathologies, including degenerative disease, disc perforation and heterotopic ossification. One barrier hindering the development of new therapies is that animal models recapitulating TMJ diseases are poorly established. The objective of this study was to develop an animal model for TMJ cartilage degeneration and disc pathology, including disc perforation and soft tissue heterotopic ossification. Methods New Zealand white rabbits (n=9 rabbits) underwent unilateral TMJ disc perforation surgery and sham surgery on the contralateral side. A 2.5 mm defect was created using a punch biopsy in rabbit TMJ disc. The TMJ condyles and discs were evaluated macroscopically and histologically after 4, 8 and 12 weeks. Condyles were blindly scored by 4 independent observers using OARSI recommendations for macroscopic and histopathological scoring of osteoarthritis in rabbit tissues. Results Histological evidence of TMJ condylar cartilage degeneration was apparent in experimental condyles following disc perforation relative to sham controls after 4 and 8 weeks, including surface fissures and loss of Safranin O staining. At 12 weeks, OARSI scores indicated experimental condylar cartilage erosion into the subchondral bone. Most strikingly, heterotopic ossification occurred within the TMJ disc upon perforation injury in 6 rabbits after 8 and 12 weeks. Conclusion We report for the first time a rabbit TMJ injury model that demonstrates condylar cartilage degeneration and disc ossification, which is indispensible for testing the efficacy of potential TMJ therapies.

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Section: Resultsmentioning

confidence: 99%

Soft tissue ossification and condylar cartilage degeneration following TMJ disc perforation in a rabbit pilot study

Embree

Iwaoka

Kong

et al. 2015

Osteoarthritis and Cartilage

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“…Moreover, data from a number of recent studies indicated that deletions of type VI and IX collagens, matrilin 3, biglycan, and fibromodulin-all of which are components of the pericellular matrix-result in early onset articular cartilage degeneration. [22][23][24] Although it is clear that the disruption of the pericellular matrix is implicated in the initiation of articular cartilage degeneration, the question remains as to how the pericellular matrix is degraded and then leads to progression characterized by loss of aggrecan and collagen in the interterritorial matrix.…”

Section: Discussionmentioning

confidence: 99%

Intact Pericellular Matrix of Articular Cartilage Is Required for Unactivated Discoidin Domain Receptor 2 in the Mouse Model

Polur

Servais

et al. 2011

The American Journal of Pathology

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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.

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“…However, a biological explanation for the propensity of females in the TMD population has not been identified. Because mouse models for both FSHD and TMD have been developed or are underway (28,29), the ability to measure the normal and pathological functional state of masticatory muscles could be utilized to assess potential therapies for these disorders.…”

Section: Discussionmentioning

confidence: 99%

Sexual dimorphism of murine masticatory muscle function

Daniels

Tian

Barton

2008

Archives of Oral Biology

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Abstract(1) Objective-To determine if gender distinctions of force generating capacity existed in murine masticatory muscles.(2) Design-In order to investigate the effect of sex on force generating capacity in this muscle group, an isolated muscle preparation was developed utilizing the murine anterior deep masseter. Age-matched male and female mice were utilized to assess function, muscle fiber type and size in this muscle.(3) Results-Maximum isometric force production was not different between age-matched male and female mice. However, the rate of force generation and relaxation was slower in female masseter muscles. Assessment of fiber type distribution by immunohistochemistry revealed a threefold decrease in the proportion of myosin heavy chain 2b positive fibers in female masseters, which correlated with the differences in contraction kinetics.(4) Conclusions-These results provide evidence that masticatory muscle strength in mice is not affected by sex, but there are significant distinctions in kinetics associated with force production between males and females.

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Mice Deficient in Biglycan and Fibromodulin as a Model for Temporomandibular Joint Osteoarthritis

Cited by 44 publications

References 67 publications

Soft tissue ossification and condylar cartilage degeneration following TMJ disc perforation in a rabbit pilot study

Soft tissue ossification and condylar cartilage degeneration following TMJ disc perforation in a rabbit pilot study

Intact Pericellular Matrix of Articular Cartilage Is Required for Unactivated Discoidin Domain Receptor 2 in the Mouse Model

Sexual dimorphism of murine masticatory muscle function

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