The Long Non-coding RNA-ORLNC1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Fate

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to differentiate into osteoblasts or adipocytes, and the shift between osteogenic and adipogenic differentiation determines bone mass. The aim of this study was to identify whether lncRNAs are involved in the differentiation commitment of BMSCs during osteoporosis. Here, we found ORLNC1, a functionally undefined lncRNA that is highly conserved, which exhibited markedly higher expression levels in BMSCs, bone tissue, and the serum of OVX-induced osteoporotic mice than sham-operated counterparts. Notably, a similar higher abundance of lncRNA-ORLNC1 expression was also observed in the bone tissue of osteoporotic patients. The transgenic mice overexpressing lncRNA-ORLNC1 showed a substantial increase in the osteoporosis-associated bone loss and decline in the osteogenesis of BMSCs. The BMSCs pretreated with lncRNA-ORLNC1-overexpressing lentivirus vector exhibited the suppressed capacity of osteogenic differentiation and oppositely enhanced adipogenic differentiation. We then established that lncRNA-ORLNC1 acted as a competitive endogenous RNA (ceRNA) for miR-296. Moreover, miR-296 was found markedly upregulated during osteoblast differentiation, and it accelerated osteogenic differentiation by targeting Pten. Taken together, our results indicated that the lncRNA-ORLNC1-miR-296-Pten axis may be a critical regulator of the osteoporosis-related switch between osteogenesis and adipogenesis of BMSCs and might represent a plausible therapeutic target for improving osteoporotic bone loss.

Long non-coding RNA MIR22HG promotes osteogenic differentiation of bone marrow mesenchymal stem cells via PTEN/ AKT pathway

“…They found HOTAIR suppressed osteogenic differentiation of rat BMSCs through inhibiting the Wnt/β-catenin pathway 30 . Yang et al demonstrated that lncRNA ORLNC1 alleviated osteoporosis by enhancing osteogenesis through the increase of BMP2 by sponging miR-140-5p 31 .…”

The roles of miRNA, lncRNA and circRNA in the development of osteoporosis

“…After si-lncRNA HOTAIR, the activity of RUNX2, COL1A1 mRNA expression and ALP would be preeminent [105]. lncRNA MIAT could regulate its binding to target genes by sponging miR-150-5p, and its overexpression inhibits osteogenic differentiation [106]. lncRNA-ORLNC1 acts as a ceRNA for miR-296, reducing the ability of this miRNA to promote osteoblast differentiation by targeting Pten [49].…”

Role of LncRNAs and CircRNAs in Bone Metabolism and Osteoporosis

“…The osteoporosis-related lncRNA 1 (ORLNC1), which was highly expressed not only in BMSCs or the serum of osteoporotic mice, but also in bone tissue of osteoporotic patients, could decrease the osteogenic differentiation of BMSCs (Yang et al, 2019). Moreover, ORLNC1 is demonstrated to be a competitive endogenous RNA (ceRNA) for miR-296, which, by targeting phosphatase and tensin homolog (PTEN), a well-known negative regulator of osteogenesis could reduce osteogenesis (Yang et al, 2019).…”