YY1-induced lncRNA XIST inhibits cartilage differentiation of BMSCs by binding with TAF15 to stabilizing FUT1 expression.

INTRODUCTION

The functional roles and mechanism of the XIST in osteoarthritis and the chondrogenic differentiation of BMSCs were clarified.

METHODS

The expression levels of XIST, TAF15, FUT1 and YY1 were detected through quantitative RT-PCR. The protein expression of Sox9, ACAN, COL2A1 and FUT1 were detected by western blot and immunohistochemistry. The damage of cartilage tissue was detected by HE staining, and Safranin O-fast green. Alcian-Blue and Alizarin red S staining were performed to evaluate BMSCs chondrogenic differentiation. The relationship between XIST and TAF15, XIST and TAF15 were analyzed by RNA immunoprecipitation assay. Luciferase reporter assays and chromatin immunoprecipitation were performed to detect the interaction relationship between XIST and YY1. In addition, osteoarthritis mice were built to assess the function of XIST .

RESULTS

The levels of XIST, TAF15 and FUT1 were upregulated in cartilage tissues from osteoarthritis patient. The level of XIST was decreased in BMSCs during chondrogenic differentiation. XIST overexpression inhibited the chondrogenic differentiation of BMSCs. Moreover, silencing of FUT1 reversed the effects of XIST overexpression on BMSCs chondrogenic differentiation. Mechanistically, in BMSCs, YY1 induced the expression of XIST in BMSCs, and XIST regulated FUT1 mRNA stability through targeting TAF15. Furthermore, silencing of XIST alleviated the symptoms of cartilage injury in OA mice.

CONCLUSION

Taken together, these results suggested that YY1 induced XIST was closely related to the chondrogenic differentiation of BMSCs and the progression of osteoarthritis by TAF15/FUT1 axis, and may be a new OA therapeutic target.