MiR-655-3p inhibits the progression of osteoporosis by targeting LSD1 and activating BMP-2/Smad signaling pathway

Abstract

Osteoporosis (OP) is one of the most common chronic metabolic bone diseases in the seniors and postmenopausal women. Plenty of microRNAs (miRNAs) have been confirmed to be involved in OP progression. However, the role of miR-655-3p in osteogenic differentiation and bone formation was still unclear. In this study, we aimed to investigate the cellular function of miR-655-3p and its underlying mechanism in OP. We found that miR-655-3p expression was downregulated in both ovariectomized (OVX) mice bone tissues and MC3T3-E1 cells treated with simulated microgravity (MG). MiR-655-3p overexpression facilitated cell differentiation but suppressed cell apoptosis of MC3T3-E1 cells induced by simulated MG. Mechanistically, we confirmed that lysine-specific histone demethylase 1 (LSD1) is a downstream target gene of miR-655-3p. Furthermore, overexpression of miR-655-3p activated the bone morphogenetic protein 2 (BMP-2)/decapentaplegic homolog (Smad) signaling pathway by suppressing LSD1 expression. Moreover, LSD1 knockdown accelerated osteogenic differentiation and inhibited apoptosis in MC3T3-E1 cells under simulated MG. Additionally, the OVX mouse model was established to investigate the role of miR-655-3p/LSD1 axis in vivo. The results demonstrated that LSD1 could reverse the effects triggered by the injection of adeno-associated virus-miR-655-3p on OP development. Further investigations revealed that miR-655-3p boosted osteogenic differentiation through LSD1/BMP-2/Smad signaling pathway. In summary, these findings implied a potential value of miR-655-3p in OP therapy.

Effect of LSD1 on osteogenic differentiation of human periodontal ligament stem cells in periodontitis

“…In addition, our results elicited that LSD1 expression was decreased in hPDLSCs undergoing osteogenic induction. Consistently, a pioneering research elucidated that LSD1 exhaustion facilitated bone formation and MSC osteogenic differentiation and sabotaged cell death (Wang, Liu, et al, 2020). Next, to elaborately explore the role of LSD1 in periodontitis, hPDLSCs were transduced with si‐LSD1 to reduce LSD1 expression, and the results supported that LSD1 knockdown accelerated osteogenic differentiation of hPDLSCs in inflammatory microenvironment as presented by the promoted levels of Runx2, OCN, and ALP.…”

Exosomal miR-655-3p inhibits growth, and invasion and macrophage M2 polarization through targeting CXCR4 in papillary thyroid carcinoma

“…Inhibition of miR-655-3p by NFIA-AS2 remarkably conduced to cell proliferation, motility, and impeded apoptosis in glioma via enhancing the expression of ZFX (Xin et al, 2020). Through targeting LSD1 to activate BMP-2/Smad pathway, miR-655-3p hindered the progression of osteoporosis (Wang et al, 2020b). In our research, we probed the function of exosomecarried miR-655-3p by transfecting miR-655-3p mimics or inhibitor into PTC cells.…”

Functional micro-RNA drugs acting as a fate manipulator in the regulation of osteoblastic death

“…It has been demonstrated that lysine-specific histone demethylase 1 (LSD1) is the downstream target gene of miR-655-3p, which further effected the BMP-2/Smad signaling to promote osteogenesis. 68 Caspase-3 is one of the most critical components in the activation of the apoptosis cascade. Therefore, downregulation of caspase-3 can block the process of apoptosis.…”