Zhang Yuelei, Weng Shiyang, Yin Junhui, Ding Hao, Zhang Changqing, Gao Youshui
Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
Mol Med Rep. 2017 May;15(5):2473-2480. doi: 10.3892/mmr.2017.6308. Epub 2017 Mar 9.
Vitamin K2 has been demonstrated to promote the osteogenic differentiation of mesenchymal stem cells; however, the mechanisms underlying this effect remain unclear. As microRNA (miR)‑133a has been identified as a negative regulator of osteogenic differentiation, the present study hypothesized that vitamin K2 promoted osteogenesis by inhibiting miR‑133a. Using human bone marrow stromal cells (hBMSCs) overexpressing miR‑133a, or a control, the expression levels of osteogenesis‑associated proteins, including runt‑related transcription factor 2, alkaline phosphatase and osteocalcin, were analyzed. miR‑133a significantly suppressed the osteogenic differentiation of hBMSCs. To determine the effect of vitamin K2 on miR‑133a expression and osteogenesis, hBMSCs were treated with vitamin K2. Vitamin K2 inhibited miR‑133a expression, which was accompanied by enhanced osteogenic differentiation. Furthermore, the expression levels of vitamin K epoxide reductase complex subunit 1, the key protein in γ‑carboxylation, were downregulated by miR‑133a overexpression and upregulated by vitamin K2 treatment, indicating a positive feedback on γ‑carboxylation. The results of the present study suggested that vitamin K2 targets miR‑133a to regulate osteogenesis.
维生素K2已被证明可促进间充质干细胞的成骨分化；然而，这种作用的潜在机制仍不清楚。由于微小RNA（miR）-133a已被确定为成骨分化的负调节因子，本研究假设维生素K2通过抑制miR-133a来促进成骨作用。使用过表达miR-133a的人骨髓基质细胞（hBMSC）或对照，分析了包括 runt相关转录因子2、碱性磷酸酶和骨钙素在内的成骨相关蛋白的表达水平。miR-133a显著抑制了hBMSC的成骨分化。为了确定维生素K2对miR-133a表达和成骨的影响，用维生素K2处理hBMSC。维生素K2抑制了miR-133a的表达，同时伴随着成骨分化的增强。此外，维生素K环氧化物还原酶复合体亚基1（γ羧化作用中的关键蛋白）的表达水平在miR-133a过表达时下调，在维生素K2处理时上调，表明对γ羧化作用存在正反馈。本研究结果表明，维生素K2靶向miR-133a来调节成骨作用。
