SNHG5/miR‐582‐5p/RUNX3 feedback loop regulates osteogenic differentiation and apoptosis of bone marrow mesenchymal stem cells

Abstract

Osteoporosis is one of the most prevailing orthopedic diseases that causes a heavy burden on public health. Given that bone marrow‐derived mesenchymal stem cells (BMSCs) are of immense importance in osteoporosis development, it is necessary to expound the mechanisms underlying BMSC osteoblastic differentiation. Although mounting research works have investigated the role of small nucleolar RNA host gene 5 (SNHG5) in various diseases, elucidations on its function in osteoporosis are still scarce. It was observed that SNHG5 and RUNX family transcription factor 3 (RUNX3) were remarkably elevated during osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). Further, we disclosed that the silencing of SNHG5 suppressed osteogenic differentiation and induced apoptosis of hBMSCs. What's more, SNHG5 acted as a competing endogenous RNA to affect RUNX3 expression via competitively binding with microRNA (miR)‐582‐5p. RUNX3 was also confirmed to simulate the transcriptional activation of SNHG5. Finally, our findings manifested that the positive feedback loop of SNHG5/miR‐582‐5p/RUNX3 executed the promoting role in the development of osteoporosis, which shed light on specific molecular mechanism governing SNHG5 in osteogenic differentiation and apoptosis of hBMSCs and indicated that SNHG5 may represent a novel target for the improvement of osteoporosis therapy.

Effects of miRNAs, lncRNAs and circRNAs on osteoporosis as regulatory factors of bone homeostasis (Review)

“…Specifically, the study concluded that GAS5 promotes OB differentiation in BMScs by regulating the uPF1/SMad7 pathway and protects against osteoporosis (55). Similarly, Zheng et al (56) reported that lncSnHG5 promoted osteogenic differentiation in hBMScs by competitively targeting mir-582-5p to regulate runX3 expression, indicating that SnHG5 may be a novel target candidate for osteoporosis therapy. MIR22HG expression was found to be significantly downregulated in BMScs from osteoporotic mice and was increased during the process of human BMSc osteogenic differentiation.…”

“…in addition to the regulation of apoptosis, it was found that lnc_000052 plays a crucial role in BMSc proliferation and migration via the mir-96-5p-PiK3r1 axis (69). Knockdown of the lncrna SnHG5 promoted apoptosis in hBMScs, and further results demonstrated that SnHG5 inhibited apoptosis through the mir-582-5p/runX3 pathway (56). Similarly, SnHG5 has been reported to play an important role in human chronic myelogenous leukaemia by inhibiting cell apoptosis (70).…”

Knockdown of hsa_circ_0001275 reverses dexamethasone-induced osteoblast growth inhibition via mediation of miR-377/CDKN1B axis

“…Based on this point, circRNAs are regarded as key mediators in multiple diseases [12,13]. In addition, circRNAs have been reported to regulate the progression of osteoporosis [14,15]. It has also been confirmed that hsa_circ_0001275 is upregulated in osteoporosis [16].…”

“…On the other hand, Runx3 is a member of the Runx family of proteins, which can regulate the markers of chondrocyte maturation [22]. Zheng J et al found Runx3 were remarkably elevated during the progression of osteoporosis [14]; Bauer O et al indicated that loss of osteoblast Runx3 could produce severe congenital osteopenia [23]. Therefore, it can be suggested that Runx3 plays a crucial role in osteoporosis.…”

The role of long noncoding RNA THAP9‐AS1 in the osteogenic differentiation of dental pulp stem cells via the miR‐652‐3p/VEGFA axis

“…Metastasis‐associated lung adenocarcinoma transcript 1 promotes osteogenic differentiation by sequestering miR‐143 and regulating osterix expression in human bone marrow‐derived mesenchymal stem cells [18]. Small nucleolar RNA host gene 5 serves as a competing endogenous RNA to promote osteogenic differentiation and inhibits apoptosis of bone marrow mesenchymal stem cells [19]. In addition, a recent study indicated that lncRNAs could act as ceRNAs during the osteogenic or odontogenic differentiation of DPSCs [20].…”