Purpose

Introduction: Mature articular cartilage displays poor intrinsic healing and its degradation is the major hallmark of osteoarthritis (OA). TGF-β is a multifunctional cytokine that plays a critical role in cartilage repair and maintenance. Aberrant TGF- β signaling in chondrocytes has been strongly implicated in the pathogenesis of OA. Our group has previously reported CD109 as a novel TGF-β co-receptor and shown that CD109 is a potent negative regulator of TGF-β signaling in the skin.

Objective: The proposed study is aimed at identifying whether manipulation of CD109 expression levels modulates the balance between TGF-β signaling via ALK1 versus ALK5 signaling pathways and regulates ECM protein expression in vivo in articular chondrocytes.

Methods and Materials

Methods: Articular cartilage tissue was collected and primary chondrocytes were isolated from CD109 KO and wild-type mice. TGF-β signaling components were analyzed in isolated chondrocytes or cartilage tissue by determining ALK5 versus ALK1 levels and Smad2/3 versus Smad1/5 levels using Western blot. Chondrocyte function was determined by evaluating the expression of, collagen type II, aggrecan, collagenase (MMP-13) and aggrecanase (ADAMTS-5), at the protein and mRNA levels by Western blot, real time PCR or immunocytochemistry (ICC).

Results

Results: CD109 KO mice markedly enhance ALK5 levels and promote expression of collagen type II, aggrecan expression in articular chondrocytes in comparison with wild-type mice. On the other hand, that loss of CD109 expression results in decreasing of ALK1 levels and inhibiting MMP13 and ADAMTS5 expression in CD109 KO mice chondrocytes. Moreover, histological results indicates that the collagen content in CD109 KO mice articular cartilage is increased significantly in comparison with wild-type mice.

Conclusion

Conclusion: Our findings suggest that CD109 differentially regulates TGF-β signaling pathways and inhibits ECM protein production while promoting proteases expression in articular chondrocytes. We conclude that CD109 may play an important role in maintaining cartilage function and integrity.