The lncRNA MCF2L-AS1 controls osteogenic differentiation by regulating miR-33a

Abstract

Bone homeostasis is maintained by balanced osteoblast-mediated tissue production and osteoclastmediated tissue destruction, and is disrupted in pathological conditions such as osteoporosis. The mechanisms underlying osteogenic differentiation of bone marrow mesenchymal stem cells, which is critical to bone homeostasis, are not completely clear, despite extensively studies. Long noncoding RNAs (lncRNAs) have recently emerged as novel therapeutic targets in various diseases. However, the expression pattern and biological function of lncRNAs in osteogenic differentiation remain unclear. In this study, we aimed to determine the role of lncRNAs in osteogenic differentiation of human bone marrow mesenchymal stem cells. We found high lncRNA MCF2L-AS1 expression in human bone marrow mesenchymal stem cells, and used bioinformatics analysis to analyze its function. MCF2L-AS1 knockdown induced inhibition of osteoblast differentiation. Silencing of MCF2L-AS1 increased the expression of miR-33a and subsequently inhibited Runx2 expression at the post-transcriptional level. Moreover, MCF2L-AS1 directly interacted with miR-33a, and downregulation of miR-33a efficiently reversed the suppression of Runx2 induced by MCF2L-AS1 short hairpin RNA (shRNA). Thus, MCF2L-AS1 positively regulated the expression of Runx2 by sponging miR-33a, and promoted osteogenic differentiation in BMSCs. Our results indicated that the lncRNA MCF2L-AS1 plays a critical role in the osteogenic differentiation of BMSCs, and targeting lncRNA MCF2L-AS1 could be a promising strategy to promote osteogenic differentiation.

Long non‑coding RNA RP11‑84C13.1 promotes osteogenic differentiation of bone mesenchymal stem cells and alleviates osteoporosis progression via the miR‑23b‑3p/RUNX2 axis

“…Although the role of RP11-84C13.1 in osteoporosis has been preliminarily studied, our current knowledge of its basic pathophysiological mechanism remains unclear. To date, multiple RNA transcripts, such as lncRNAs and circular RNAs, have been revealed to function as competitive endogenous RNAs by miRNA binding ( 26 , 27 ). Wang et al ( 28 ) revealed that lncRNA KCNQ1OT1 promoted BMP2 expression to regulate osteogenic differentiation by sponging miRNA-214.…”

Role of LncRNAs and CircRNAs in Bone Metabolism and Osteoporosis

“…This could lead to inhibition of osteoblast differentiation. Thus, MCF2L-AS1 stimulated osteogenic differentiation in BMSCs by positively regulating the expression of Runx2 (Chen et al, 2020).…”

The Involvement of Long Non-Coding RNAs in Bone

“…Chen et al [56] studied the role of lncRNA MCF2L-AS1 in BMSC osteogenic differentiation and the underlying molecular mechanisms. Microarray analysis was performed to detect lnRNA expression during the hBMSC osteoinduction, identifying nine upregulated lncRNAs and fifteen downregulated lncRNAs, according to the absolute fold change ≥ 1.5 and p-value ≤ 0.05.…”