Long non-coding RNA XIST promotes osteoporosis through inhibiting bone marrow mesenchymal stem cell differentiation

The purpose of the present study was to identify the key long non-coding (lnc)RNAs in the occurrence and development of osteoporosis (OP) and to explore the associated molecular mechanism. First, the Gene Expression Omnibus (GEO) datasets, with key words 'osteoporosis' and 'HG-133A', were screened. RankProd R package was used to calculate the dysregulated lncRNAs in OP. Following this, bone marrow mesenchymal stem cells (BM-MSCs) harvested from 3-week-old Sprague Dawley rats were employed for detection of osteoblast differentiation. Following overexpression or interference with X-inactive specific transcript (XIST), osteogenesis-associated genes and proteins in BM-MSCs were detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Alkaline phosphatase (ALP) and Alizarin Red S staining were also performed to measure the osteogenic ability of BM-MSCs. Results from the two datasets indicated that 6 lncRNAs were dysregulated in OP. Notably, XIST is key lncRNA in diverse diseases, and was subsequently selected for analysis. It was revealed that XIST was significantly upregulated in plasma and monocytes from patients with OP compared with the normal controls. Furthermore, results indicated that overexpression of XIST significantly inhibited osteoblast differentiation in BM-MSCs, as evidenced by the decreased expression of ALP, bone γ-carboxyglutamic acid-containing protein and runt related transcription factor 2, reduced ALP activity and a decreased number of calcium deposits. However, interference of XIST exhibited the opposite biological effects in BM-MSCs. Taken together, XIST was highly expressed in the serum and monocytes of patients with OP. In addition, the findings suggested that XIST could inhibit osteogenic differentiation of BM-MSCs.