Rheumatoid arthritis (RA), a chronic autoimmune disease, affects around 1% population worldwide, with the life quality of patients severely reduced. In this study, it is intended to explore the role of long non-coding RNA X-inactive specific transcript (lncRNA XIST) in RA and the underlying mechanisms associated with let-7c-5p and signal transducer and activator of transcription 3 (STAT3).
LncRNA XIST, let-7c-5p, and STAT3 expressions were determined in RA and normal cartilage tissues, and their relationship was analyzed in osteoblasts. The regulatory effects of lncRNA XIST in RA were investigated when XIST expression was upregulated or downregulated in osteoblasts. TNF-α, IL-2, IL-6, alkaline phosphatase (ALP), osteocalcin, TGF-β1, and IGF1 were measured in vivo in RA rats.
LncRNA XIST and STAT3 were expressed at high levels and let-7c-5p expressed at a low level in RA cartilage tissues. LncRNA XIST silencing or let-7c-5p enhancement led to decreased levels of TNF-α, IL-2, and IL-6, suggestive of suppressed inflammatory response, and increased levels of ALP, osteocalcin, TGF-β1, and IGF-1 as well as reduced damage in cartilage tissues.
LncRNA XIST downregulation could promote proliferation and differentiation of osteoblasts in RA, serving as a future therapeutic target for RA.