Long Non-coding RNA Taurine Upregulated Gene 1 is Downregulated in Osteoporosis and Influences the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

Overview

Journal PeerJ

Specialties Biology
Environmental Health
General Medicine

Date 2021 May 12

PMID 33976977

Citations 7

Authors

Zhaowei Teng

Yun Zhu

Qinggang Hao

Xiaochao Yu

Yirong Teng

Qiaoning Yue

Xiguang Zhang

Sheng Lu

Affiliations

Soon will be listed here.

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.

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References

Zhang W, Chen L, Wu J, Li J, Zhang X, Xiang Y . Long noncoding RNA TUG1 inhibits osteogenesis of bone marrow mesenchymal stem cells via Smad5 after irradiation. Theranostics. 2019; 9(8):2198-2208. PMC: 6531293. DOI: 10.7150/thno.30798. View

Zhang H, Du X, Dong Q . LncRNA XIXT promotes osteogenic differentiation of bone mesenchymal stem cells and alleviates osteoporosis progression by targeting miRNA-30a-5p. Eur Rev Med Pharmacol Sci. 2019; 23(20):8721-8729. DOI: 10.26355/eurrev_201910_19266. View

He Q, Yang S, Gu X, Li M, Wang C, Wei F . Long noncoding RNA TUG1 facilitates osteogenic differentiation of periodontal ligament stem cells via interacting with Lin28A. Cell Death Dis. 2018; 9(5):455. PMC: 5908786. DOI: 10.1038/s41419-018-0484-2. View

Johnson R, Leopold J, Loscalzo J . Vascular calcification: pathobiological mechanisms and clinical implications. Circ Res. 2006; 99(10):1044-59. DOI: 10.1161/01.RES.0000249379.55535.21. View

Shen W, Chen J, Gantz M, Punyanitya M, Heymsfield S, Gallagher D . MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older adults. Eur J Clin Nutr. 2012; 66(9):983-8. PMC: 3396793. DOI: 10.1038/ejcn.2012.35. View

Ramirez-Salazar E, Carrillo-Patino S, Hidalgo-Bravo A, Rivera-Paredez B, Quiterio M, Ramirez-Palacios P . Serum miRNAs miR-140-3p and miR-23b-3p as potential biomarkers for osteoporosis and osteoporotic fracture in postmenopausal Mexican-Mestizo women. Gene. 2018; 679:19-27. DOI: 10.1016/j.gene.2018.08.074. View

Liu S, Sun Q, Qiao X, Li X, Yang J, Wang T . LncRNA TUG1 influences osteoblast proliferation and differentiation through the Wnt/β-catenin signaling pathway. Eur Rev Med Pharmacol Sci. 2019; 23(11):4584-4590. DOI: 10.26355/eurrev_201906_18035. View

Manolagas S . Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000; 21(2):115-37. DOI: 10.1210/edrv.21.2.0395. View

Katsushima K, Natsume A, Ohka F, Shinjo K, Hatanaka A, Ichimura N . Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment. Nat Commun. 2016; 7:13616. PMC: 5150648. DOI: 10.1038/ncomms13616. View

10.

Johnell O, Kanis J . An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006; 17(12):1726-33. DOI: 10.1007/s00198-006-0172-4. View

11.

Moerman E, Teng K, Lipschitz D, Lecka-Czernik B . Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell. 2004; 3(6):379-89. PMC: 1850101. DOI: 10.1111/j.1474-9728.2004.00127.x. View

12.

Cai H, Liu X, Zheng J, Xue Y, Ma J, Xi Z . Long non-coding RNA taurine upregulated 1 enhances tumor-induced angiogenesis through inhibiting microRNA-299 in human glioblastoma. Oncogene. 2016; 36(3):318-331. DOI: 10.1038/onc.2016.212. View

13.

Wu Q, Li X, Miao Z, Ye J, Wang B, Zhang F . Long Non-coding RNAs: A New Regulatory Code for Osteoporosis. Front Endocrinol (Lausanne). 2018; 9:587. PMC: 6186991. DOI: 10.3389/fendo.2018.00587. View

14.

Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M . A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011; 147(2):358-69. PMC: 3234495. DOI: 10.1016/j.cell.2011.09.028. View

15.

Wang L, Wang Y, Li Z, Li Z, Yu B . Differential expression of long noncoding ribonucleic acids during osteogenic differentiation of human bone marrow mesenchymal stem cells. Int Orthop. 2015; 39(5):1013-9. DOI: 10.1007/s00264-015-2683-0. View

16.

Kanis J . Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int. 1994; 4(6):368-81. DOI: 10.1007/BF01622200. View

17.

Song W, Gu W, Qian Y, Ma X, Mao Y, Liu W . Identification of long non-coding RNA involved in osteogenic differentiation from mesenchymal stem cells using RNA-Seq data. Genet Mol Res. 2016; 14(4):18268-79. DOI: 10.4238/2015.December.23.14. View

18.

Chen C, Tang Z, Song Q, Yang M, Shi Q, Weng Y . Downregulated microRNA-23b promotes BMP9-mediated osteogenesis in C2C12 myoblast cells by targeting Runx2. Mol Med Rep. 2016; 13(3):2492-8. PMC: 4768947. DOI: 10.3892/mmr.2016.4814. View

19.

Komori T . Regulation of osteoblast differentiation by transcription factors. J Cell Biochem. 2006; 99(5):1233-9. DOI: 10.1002/jcb.20958. View

20.

Fu L, Peng S, Wu W, Ouyang Y, Tan D, Fu X . LncRNA HOTAIRM1 promotes osteogenesis by controlling JNK/AP-1 signalling-mediated RUNX2 expression. J Cell Mol Med. 2019; 23(11):7517-7524. PMC: 6815819. DOI: 10.1111/jcmm.14620. View