Fang Tao, Zhang Ranxi, Song Feng, Chu Xueru, Fu Qin, Wu Qianqian
Department of Orthopedic Surgery, Qingdao Municipal Hospital, Qingdao, Shandong, 266000, China.
Department of Spine Surgery, Qingdao Municipal Hospital, Qingdao, Shandong, 266000, China.
J Orthop Surg Res. 2024 Dec 30;19(1):887. doi: 10.1186/s13018-024-05410-7.
An improved understanding of the molecular actions underpinning bone marrow mesenchymal stem cell (BMSC) differentiation could highlight new therapeutics for osteoporosis (OP). Current evidence indicates that microRNAs (miRNAs) exert critical roles in many biological systems, including osteoblast differentiation. In this study, we examined miR-468-3p effects on osteogenic differentiation (OD). Distinct miR-468-3p reductions were identified during OD. MiR-468-3p also suppressed BMSC OD in gain- and loss-of-function assays, while it negatively regulated Runx2 as shown by molecular, protein, and bioinformatics approaches. When Runx2 was inhibited by small-interfering RNA (siRNA), the inhibitory effects of miR-468-3p toward BMSC osteogenesis were considerably reversed. Also, silenced miR-468-3p in ovariectomized (OVX) and sham mice augmented bone mass (BM) and bone formation (BF) and improved trabecular (Tb) microarchitecture. Therefore, miR-468-3p is a novel Runx2 regulator with key physiological action in BF and OD.
对骨髓间充质干细胞（BMSC）分化的分子机制有更深入的了解，可能会为骨质疏松症（OP）带来新的治疗方法。目前的证据表明，微小RNA（miRNA）在包括成骨细胞分化在内的许多生物系统中发挥着关键作用。在本研究中，我们检测了miR-468-3p对成骨分化（OD）的影响。在OD过程中发现了明显的miR-468-3p表达降低。在功能获得和功能丧失实验中，miR-468-3p也抑制了BMSC的OD，而分子、蛋白质和生物信息学方法显示它对Runx2有负调控作用。当Runx2被小干扰RNA（siRNA）抑制时，miR-468-3p对BMSC成骨的抑制作用被显著逆转。此外，在去卵巢（OVX）和假手术小鼠中沉默miR-468-3p可增加骨量（BM）和骨形成（BF），并改善小梁（Tb）微结构。因此，miR-468-3p是一种新型的Runx2调节剂，在BF和OD中具有关键的生理作用。
