Teng Zhaowei, Zhu Yun, Hao Qinggang, Yu Xiaochao, Teng Yirong, Yue Qiaoning, Zhang Xiguang, Lu Sheng
The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, Yunan, China.
Yunnan Key Laboratory of Digital Orthopedics, The First People's Hospital of Yunnan Province, Kunming, Yunan, China.
PeerJ. 2021 Apr 20;9:e11251. doi: 10.7717/peerj.11251. eCollection 2021.
With aging, an imbalance in bone remodeling leading to increased bone resorption and decreased bone formation is thought to contribute to osteoporosis. Osteoblastic differentiation of bone marrow mesenchymal stem cells (BMMSCs) plays a vital role in the pathogenesis of osteoporosis. However, the detailed molecular mechanisms of osteoporosis remain incompletely understood. Given that long non-coding RNA taurine upregulated gene 1 (lnc TUG1) plays a critical role in the osteogenic differentiation, and microRNA-23b (miR-23b) as a putative sponge for lnc TUG1 has upregulated expression in osteoporosis. Therefore, this study investigated the roles of TUG1/miR-23b in osteoporotic pathology.
TUG1 and miR-23b expression in the plasma of osteoporotic patients were evaluated by quantitative real-time PCR (qRT-PCR). The osteogenic differentiation in human BMMSCs was evaluated by qRT-PCR, western blot, Alizarin red staining after knockdown of TUG1 by small interfering RNA (siRNA) treatment.
Decreased expression of TUG1 and increased expression of miR-23b evident in the plasma of patients with osteoporosis than in that of age- and sex-matched healthy controls. Additionally, increased miR-23b expression inhibited runt-related transcription factor 2 (RUNX2), osteocalcin, and osteopontin expression and reduced calcified nodule formation based on the results of qRT-PCR, western blot, and Alizarin Red S staining.
The study for the first time reported that silence of lncRNA TUG1 significantly suppressed the osteogenic differentiation of BMMSCs possibly by targeting the miR-23b/RUNX2 signaling pathway. This mechanism of TUG1/miR-23b/RUNX2 signaling within the osteogenic differentiation of BMMSCs might provide new insight for the development of lncRNA-directed diagnostic and therapeutic strategies for osteoporosis.
随着年龄增长，骨重塑失衡导致骨吸收增加和骨形成减少，被认为是骨质疏松症的成因。骨髓间充质干细胞（BMMSCs）的成骨细胞分化在骨质疏松症的发病机制中起关键作用。然而，骨质疏松症的详细分子机制仍未完全明确。鉴于长链非编码RNA牛磺酸上调基因1（lnc TUG1）在成骨分化中起关键作用，且作为lnc TUG1假定海绵体的微小RNA-23b（miR-23b）在骨质疏松症中表达上调。因此，本研究探讨了TUG1/miR-23b在骨质疏松症病理过程中的作用。
采用定量实时聚合酶链反应（qRT-PCR）评估骨质疏松症患者血浆中TUG1和miR-23b的表达。通过qRT-PCR、蛋白质免疫印迹法以及用小干扰RNA（siRNA）处理敲低TUG1后进行茜素红染色，评估人BMMSCs的成骨分化。
与年龄和性别匹配的健康对照相比，骨质疏松症患者血浆中TUG1表达降低，miR-23b表达增加。此外，基于qRT-PCR、蛋白质免疫印迹法和茜素红S染色结果，miR-23b表达增加抑制了 runt相关转录因子2（RUNX2）、骨钙素和骨桥蛋白的表达，并减少了钙化结节形成。
本研究首次报道lncRNA TUG1沉默可能通过靶向miR-23b/RUNX2信号通路显著抑制BMMSCs的成骨分化。BMMSCs成骨分化过程中TUG1/miR-23b/RUNX2信号通路的这一机制可能为开发针对骨质疏松症的lncRNA导向诊断和治疗策略提供新的见解。
