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The transcription factor SOX9 is important in maintaining the chondrocyte phenotype. To identify novel genes regulated by SOX9 we investigated changes in gene expression by microarray analysis following retroviral transduction with  SOX9  of a human chondrocytic cell line (SW1353). From the results the expression of a group of genes ( SRPX ,  S100A1 ,  APOD ,  RGC32 ,  CRTL1 ,  MYBPH ,  CRLF1  and  SPINT1 ) was evaluated further in human articular chondrocytes (HACs). First, the same genes were investigated in primary cultures of HACs following  SOX9  transduction, and four were found to be similarly regulated ( SRPX ,  APOD ,  CRTL1  and  S100A1 ). Second, during dedifferentiation of HACs by passage in monolayer cell culture, during which the expression of SOX9 progressively decreased, four of the genes ( S100A1 ,  RGC32 ,  CRTL1  and  SPINT1 ) also decreased in their expression. Third, in samples of osteoarthritic (OA) cartilage, which had decreased  SOX9  expression compared with age-matched controls, there was decreased expression of  SRPX, APOD, RGC32, CRTL1  and  SPINT1 . The results showed that a group of genes identified as being upregulated by SOX9 in the initial SW1353 screen were also regulated in expression in healthy and OA cartilage. Other genes initially identified were differently expressed in isolated OA chondrocytes and their expression was unrelated to changes in SOX9. The results thus identified some genes whose expression appeared to be linked to SOX9 expression in isolated chondrocytes and were also altered during cartilage degeneration in osteoarthritis.

SOX9 transduction of a human chondrocytic cell line identifies novel genes regulated in primary human chondrocytes and in osteoarthritis