State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
J Cell Physiol. 2014 Oct;229(10):1494-502. doi: 10.1002/jcp.24591.
The elucidation of the molecular mechanisms that govern the differentiation of bone marrow stromal cells (BMSCs) could provide new insight into the treatment of bone loss diseases. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression during stem cell growth, proliferation, and differentiation. In the present study, we showed that miR-338-3p expression was significantly down-regulated during the osteoblastic differentiation of BMSCs. Additionally, miR-338-3p was up-regulated in ovariectomized (OVX) mice compared with sham mice. An in vitro analysis revealed that the over-expression of miR-338-3p can inhibit the expression of osteoblast differentiation markers such as Osterix (Osx), thus reducing osteoblast differentiation. Bioinformatic analysis and dual luciferase assays confirmed that miR-338-3p can repress gene expression by targeting Runx2 and Fgfr2. In the BMSCs derived from OVX mice, the inhibition of miR-338-3p partially rescued mineralization and osteoblast differentiation. Taken together, our data show that miR-338-3p plays an important role during osteoblast differentiation of BMSCs and serves as a potential modulator of osteoporosis via its effect on osteoblasts.
阐明调控骨髓基质细胞（BMSCs）分化的分子机制，可以为治疗骨质疏松症提供新的见解。微小 RNA（miRNA）是一种小的非编码 RNA，在干细胞生长、增殖和分化过程中调节基因表达。在本研究中，我们发现 miR-338-3p 的表达在 BMSCs 的成骨分化过程中显著下调。此外，与假手术组相比，去卵巢（OVX）小鼠中 miR-338-3p 表达上调。体外分析表明，miR-338-3p 的过表达可以抑制成骨分化标志物如 Osx 的表达，从而减少成骨细胞分化。生物信息学分析和双荧光素酶报告基因实验证实，miR-338-3p 可以通过靶向 Runx2 和 Fgfr2 来抑制基因表达。在 OVX 小鼠来源的 BMSCs 中，抑制 miR-338-3p 部分挽救了矿化和成骨分化。综上所述，我们的数据表明，miR-338-3p 在 BMSCs 的成骨分化过程中发挥重要作用，通过对成骨细胞的作用，成为骨质疏松症的潜在调节剂。
