Long non-coding RNA, Bmcob, regulates osteoblastic differentiation of bone marrow mesenchymal stem cells.

Disordered osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) contributes to bone loss. The underlying mechanisms are complicated and not fully understood. Long non-coding RNAs (lncRNAs) are emerging as an important regulatory factors on bone metabolism. Here, we discovered a novel lncRNA, Bmcob, which modulated osteogenic differentiation of primary mouse BMSCs. Expression levels of Bmcob were significantly upregulated in early-to-mid stages during osteoblast differentiation. Silencing of Bmcob suppressed osteoblastic differentiation of BMSCs in vitro, whereas its overexpression protected BMSCs from oxidative stress induced inhibition on osteogenesis. Subsequently, we discovered that selenoprotein P (Sepp1), which is located next to the Bmcob gene, was partly responsible for the regulatory effects of Bmcob. In addition, a series of selenoproteins were downregulated in BMSCs with Bmcob knockdown. Mechanistically, we found Bmcob was associated with selenocysteine insertion sequence binding protein 2 (SBP2), a critical trans-acting factor for selenoprotein synthesis. Finally, we suggest an explanatory hypothesis that through modulating nucleocytoplasmic shuttling of SBP2, Bmcob regulates a number of selenoproteins expression, including sepp1, and then mediates osteogenesis of BMSCs. Taken together, our results revealed a novel mechanism regulating osteogenesis of BMSCs and may function as a potential target for treating osteoporosis.