Sox4 is involved in osteoarthritic cartilage deterioration through induction of ADAMTS4 and ADAMTS5

What is it about?

Osteoarthritis is a common joint disease affecting approximately 250 million people worldwide, which frequently leads to rigidity and loss of motility in the elderly. Because the molecular pathogenesis of osteoarthritis remains elusive, early diagnostic markers and effective therapeutic agents have not been developed. To understand the molecular mechanisms, we attempted to identify transcription factors involved in osteoarthritis onset. Microarray analysis of mouse articular cartilage superficial zone (SFZ) cells stimulated with retinoic acid (RA) was performed to identify candidate transcription factors exhibiting highly elevated expression in response to RA. Isolated transcription factors were subsequently overexpressed in a mouse mesenchymal cell line, C3H10T1/2, and human chondrogenic cell line, SW1353. To evaluate effects of isolated transcription factors on articular cartilage destruction, mouse femoral head cartilage was infected with adenoviruses containing these factors and examined by Safranin O/Fast Green staining and immunohistochemical analysis using an anti-Adamts5 antibody. Finally, mRNA expression of isolated transcription factors was assessed in cartilage from osteoarthritis patients. Sox4, a SoxC family member transcription factor, was clearly increased in SFZ cells treated with RA. Overexpression of Sox4 or Sox11, another SoxC family member, induced ADAMTS4 and ADAMTS5 expression in both C3H10T1/2 and SW1353 cells. Ex vivo experiments showed increased ADAMTS5 expression by Sox4 or Sox11 overexpression. Furthermore, SOX4 and SOX11 mRNA expression was higher in the cartilage of osteoarthritis patients compared with non- osteoarthritis patients.

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