Long non-coding RNA taurine upregulated gene 1 is downregulated in osteoporosis and influences the osteogenic differentiation of bone marrow mesenchymal stem cells

Zhaowei Teng; Yun Zhu; Qinggang Hao; Xiaochao Yu; Yirong Teng; Qiaoning Yue; Xiguang Zhang; Sheng Lu

doi:10.7717/peerj.11251

Long non-coding RNA taurine upregulated gene 1 is downregulated in osteoporosis and influences the osteogenic differentiation of bone marrow mesenchymal stem cells

PeerJ. 2021 Apr 20:9:e11251. doi: 10.7717/peerj.11251. eCollection 2021.

Authors

Zhaowei Teng^{1

2

3}, Yun Zhu¹, Qinggang Hao¹, Xiaochao Yu¹, Yirong Teng¹, Qiaoning Yue¹, Xiguang Zhang¹, Sheng Lu^{2

3}

Affiliations

¹ The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, Yunan, China.
² Yunnan Key Laboratory of Digital Orthopedics, The First People's Hospital of Yunnan Province, Kunming, Yunan, China.
³ Kunming Medical University, The 920th Hospital, Kunming, Kunming, Yunan, China.

Abstract

Background: 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.

Material and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: LncRNA TUG1; Osteogenic differentiation; Osteoporosis; TUG1/miR-23b/RUNX2 signaling pathway; miR-23b.

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant no. 81860167, 82060167, 81960268), and the Joint special fund of Applied Fundamental Research of Kunming Medical University granted by Science and Technology Office of Yunnan (grant no. 2018FE001(-175), 2018FE001(-174), 2019FE001 (-171) 202001AY070001-097. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.