Wang Rui, Zhang Miao, Hu Ying, He Juan, Lin Qiao, Peng Nianchun
Department of Endocrinology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
Hum Cell. 2022 Nov;35(6):1671-1683. doi: 10.1007/s13577-022-00764-8. Epub 2022 Aug 10.
Osteoporosis is a disorder characterized by reduced bone mass, disruption of bone microarchitecture, and a propensity to fracture. The osteogenic differentiation of human bone mesenchymal stromal cells (hBMSCs) exerts a critical effect on preventing bone loss during osteoporosis. Herein, the study recognized miR-100-5p as a deregulated miRNA during osteoporosis (upregulated) and BMSC osteogenic differentiation (downregulated). miR-100-5p was upregulated in osteoporosis patients-isolated BMSCs compared to non-osteoporosis trauma patients-isolated BMSCs. hBMSCs, overexpression inhibited hBMSC proliferation and osteogenic differentiation, whereas miR-100-5p inhibition exerted opposite effects. TMEM135 was downregulated in osteoporosis and upregulated in differentiated osteoblasts, as well as downregulated upon the overexpression of miR-100-5p. MiR-100-5p directly targeted and inhibited TMEM135. In hBMSCs, TMEM135 silencing also inhibited hBMSC osteogenic differentiation. When co-transfected to hBMSCs, antagomir-100-5p promoted, whereas TMEM135 silencing inhibited hBMSC osteogenic differentiation; TMEM135 knockdown dramatically attenuated the effects of miR-100-5p inhibition. Taken together, miR-100-5p forms a regulatory axis with TMEM135 by direct binding. The miR-100-5p/TMEM135 axis modulates hBMSC differentiation into osteoblast. Considering the critical effect of BMSC osteogenesis on osteoporosis, this axis might play a role in osteoporosis, and further in vivo and clinical investigations are required.
骨质疏松症是一种以骨量减少、骨微结构破坏和骨折倾向为特征的疾病。人骨髓间充质基质细胞（hBMSCs）的成骨分化对预防骨质疏松症期间的骨质流失起着关键作用。在此，该研究发现miR-100-5p是骨质疏松症（上调）和BMSC成骨分化（下调）过程中失调的一种微小RNA。与非骨质疏松性创伤患者分离的BMSCs相比，骨质疏松症患者分离的BMSCs中miR-100-5p上调。hBMSCs中，miR-100-5p过表达抑制hBMSC增殖和成骨分化，而抑制miR-100-5p则产生相反的效果。TMEM135在骨质疏松症中下调，在分化的成骨细胞中上调，并且在miR-100-5p过表达时下调。miR-100-5p直接靶向并抑制TMEM135。在hBMSCs中，沉默TMEM135也抑制hBMSC成骨分化。当共转染至hBMSCs时，抗miR-100-5p促进hBMSC成骨分化，而沉默TMEM135则抑制hBMSC成骨分化；敲低TMEM135显著减弱了抑制miR-100-5p的作用。综上所述，miR-100-5p通过直接结合与TMEM135形成一个调控轴。miR-100-5p/TMEM135轴调节hBMSC向成骨细胞的分化。鉴于BMSC成骨对骨质疏松症的关键作用，该轴可能在骨质疏松症中发挥作用，需要进一步的体内和临床研究。
