MicroRNA-125b suppresses the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

Abstract

The regressive biological function of human bone marrow‑derived mesenchymal stem cells (hBMSCs) is one of the key factors resulting in the decrease of bone mass in senile osteoporosis. MicroRNAs (miRs) are non‑coding small RNAs involved in various gene regulation processes. Whether any miR(s) are involved in the progression of osteoporosis by regulating the biological function of hBMSCs remains to be elucidated. The present study aimed to compare the expression levels of miR‑125b in hBMSCs derived from senile osteoporotic patients with that of control (normal) subjects. A significantly upregulated expression of miR‑125b in osteoporotic hBMSCs was detected. To elucidate the biological function of miR‑125b in senile osteoporosis, the effects of miR‑125b expression on proliferation and osteogenic differentiation of hBMSCs were assessed using gain‑ and loss‑of‑function studies. It was evident that the overexpression of a miR‑125b mimic was able to suppress the proliferative and osteogenic differentiation of senile hBMSCs. In contrast, repression of the function of miR‑125b by transfection of an miR‑125b inhibitor promoted the proliferation and osteogenic differentiation of hBMSCs. Furthermore, the potential target gene of miR‑125b, osterix (Osx), was examined. The results of the present study strongly suggested that miR‑125b may regulate osteogenic differentiation of hBMSCs through the modulation of Osx expression.

Analysis of the Bone MicroRNome in Osteoporotic Fractures

“…A number of investigators have used in vitro culture systems and animal models trying to elucidate the role of some miRNAs in the regulation of bone cell activity [6,10,[21][22][23][24][25][26][27][28][29]. However, only scarce data are available about the involvement of miRNAs in common human skeletal disorders, such as osteoporosis and osteoarthritis.…”

microRNA Regulation of Skeletal Development

“…miR-125b, a miRNA identified in MSCs throughout many genetic screens [98,81], is predicted to target Osx. However, a relationship has not been confirmed beyond the finding of reduced Osx mRNA [99]. In contrast, miR-143 [100,101], miR-145 [100], miR-214 [102] and miR-637 [103] suppress osteogenic differentiation by directly targeting Osx.…”

MicroRNAs in Bone Balance and Osteoporosis

“…Many studies have reported that the expression of particular miRNAs in osteoblast differentiation appears upregulated or downregulated [Meng et al, 2015;Huszar and Payne, 2014;Cheung et al, 2014;Sun et al, 2014a,b;Wei et al, 2014Wei et al, , 2015Mei et al, 2013;Hwang et al, 2014;Xie et al, 2014;Xu et al, 2013;Guan et al, 2015;Jeong et al, 2014;Hu et al, 2015;Sun et al, 2015;Ding et al, 2015;Qadir et al, 2015;Zuo et al, 2015;Qu et al, 2014;Liu et al, 2014a;Chen et al, 2014b;Hupkes et al, 2014;Liao et al, 2014;Roberto et al, 2014;You et al, 2014;Kang et al, 2015;Kureel et al, 2014;Wang et al, 2015;Guo et al, 2014a;Qiao et al, 2014]. To study the role of miRNAs in human bone marrow-derived multipotent mesenchymal cells (hMSCs) differentiation to osteoblast, Oskowitz et al [2008] inhibited the miRNA master regulators, Drosha, a Class 2 ribonuclease III enzyme and Dicer, enzymes that process early transcripts to miRNA using a lentiviral-based tetracycline inducible shRNA.…”

“…With osteoclast differentiation factor (RANKL), macrophage colony stimulating factor (M-CSF) and other positive stimulating factor, mononuclear cells began to differentiate into osteoclasts [Zhao and Ivashkiv, 2011]. Compare to osteoblasts, miRNA effects on osteoclast differentiation have been less well studied Franceschetti et al, 2013;Mizoguchi et al, 2013;Lee et al, 2013;Guo et al, 2014b;Chen et al, 2014b;Shibuya et al, 2013;Nakasa et al, 2011;Roberto et al, 2015] (Table 2).…”