The biglycan/fibromodulin double knockout mice develop accelerated temporomandibular joint osteoarthritis

Objective: Biglcyan (BGN) and fibromodulin (FBN) are proteoglycans that are highly expressed in cartilage and bone. Mice doubly deficient (DKO) in BGN and FBN develop premature osteoarthritis (OA) in their knee joints. OA can also affect the temporomandibular joint (TMJ), however there are few spontaneous animal models that develop accelerated TMJ OA. Our goal was to analyze the structure of the TMJ in BGN/FBN DKO mice to determine whether they acquire premature TMJ OA. Methods: The localization and expression of BGN and FBN was determined by immunohistochemistry in WT mouse TMJ. WT and BGN/FBN DKO mouse TMJs were evaluated histologically at 3, 6, 9, and 18 months. The proliferation of condylar cartilage cells was analyzed via proliferating cellular nuclear antigen (PCNA) staining. Results: At 3 months, immunohistochemistry showed BGN and FBN co-ordinately expressed in the WT mouse TMJ articular cartilage. At this age, PCNA staining showed a significant decrease in condylar chondrocyte proliferation in the BGN/FBN DKO compared to WT control mice, but no histological differences in the tissue structure integrity were noted. At 6 months, early histopathological features of osteoarthritis were observed in the BGN/FBN DKO strain including formation of acellular regions, vertical clefts, and cellular clusters in the cartilage. By 9 months, marked evidence of TMJ OA in the BGN/FBN DKO became clear where vertical clefts extended deeper in the cartilage and nearly all condylar cartilage cells formed clusters. By 18 months, condylar cartilage integrity and cellular columnar organization was completely lost in the BGN/FBN DKO. Conclusion: Mice doubly deficient in BGN and FBN develop accelerated TMJ osteoarthritis. This unique mouse line could be used to understand the underlying molecular mechanisms of the disease and may provide insight for developing early detection methods essential for the diagnosis and prevention of TMJ osteoarthritis.