Effect of adiponectin on ATDC5 proliferation, differentiation and signaling pathways

Adiponectin, an adipose-secreted adipocytokine, exhibits various metabolic functions but has no known effect on bone development through the growth plate and specifically, in chondrocytes. Using the mouse ATDC5 cell line, a widely used in vitro model of chondrogenesis, we demonstrated the expression of adiponectin and its receptors during chondrogenic differentiation. Adiponectin at 0.5 μg/ml increased chondrocyte proliferation, proteoglycan synthesis and matrix mineralization, as reflected by upregulation of the expression of type II collagen, aggrecan, Runx2 and type X collagen, and of alkaline phosphatase activity. Quantitative RT-PCR and gelatin zymography showed a significant increase in the matrix metalloproteinase MMP9's expression and activity following adiponectin treatment. We therefore concluded that adiponectin can directly stimulate chondrocyte proliferation and differentiation. To evaluate the underlying mechanisms, we examined the effect of adiponectin on the expression of chondrogenic signaling molecules: Ihh, PTHrP, Ptc1, FGF18, BMP7, IGF1 and p21 were all upregulated while FGF9 was downregulated. This study reveals novel and direct activity of adiponectin in chondrocytes, suggesting its positive effects on bone development.