Abstract
LncRNA TUG1 has the potential to promote the osteogenic differentiation of several cells, but the role of lncRNA TUG1 in osteogenic differentiation of tendon stem/progenitor cells (TSPCs) is still unknown. This study aims to determine the role of lncRNA TUG1 in osteogenic differentiation of TSPCs. bFGF, RUNX2, and Osterix protein expressions were detected by western blot. LncRNA TUG1 and bFGF expression was detected by qRT-PCR. RNA immunoprecipitation (RIP) assay was used to confirm the interaction between TUG1 and bFGF2. Ubiquitination assay was used to determine the ubiquitination of bFGF protein. During osteogenic differentiation, the protein expression of bFGF was significantly downregulated in TSPCs, and the expression of TUG1 was significantly elevated in TSPCs. Interfering TUG1 or overexpressing bFGF suppressed osteogenic differentiation of TSPCs. In addition, lncRNA TUG1 interacted with bFGF, and lncRNA TUG1 promoted the ubiquitination of bFGF protein. We also determined that lncRNA TUG1 downregulated bFGF protein expression through promoting the ubiquitination of bFGF. LncRNA TUG1 promoted the osteogenic differentiation of TSPCs through promoting bFGF ubiquitination.
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References
Clarke SA, Brooks RA, Lee PTH, Rushton N (2004) The effect of osteogenic growth factors on bone growth into a ceramic filled defect around an implant. J Orthop Res 22(5):1016–1024
He Q, Yang S, Gu X, Li M, Wang C, Wei F (2018) Long noncoding RNA TUG1 facilitates osteogenic differentiation of periodontal ligament stem cells via interacting with Lin28A. Cell Death Dis 9(5):455–455
Honda H, Gotoh M, Kanazawa T, Ohzono H, Nakamura H, Ohta K, Nakamura K-I, Fukuda K, Teramura T, Hashimoto T et al (2017) Hyaluronic acid accelerates tendon-to-bone healing after rotator cuff repair. Am J Sports Med 45(14):3322–3330
Lee CH, Lee FY, Tarafder S, Kao K, Jun Y, Yang G, Mao JJ (2015) Harnessing endogenous stem/progenitor cells for tendon regeneration. J Clin Invest 125(7):2690–2701
Liu S, Qin M, Hu C, Wu F, Cui W, Jin T, Fan C (2013) Tendon healing and anti-adhesion properties of electrospun fibrous membranes containing bFGF loaded nanoparticles. Biomaterials 34(19):4690–4701
Luo W, Yu Y, Wang R, He D, Wang C, Zeng X, Chen X, Tan X, Huang T, Wu X (2014) P7 peptides targeting bFGF sensitize colorectal cancer cells to CPT-11. Int J Mol Med 33(1):194–200
Ni W, Zhang Y, Zhan Z, Ye F, Liang Y, Huang J, Chen K, Chen L, Ding Y (2017) A novel lncRNA uc.134 represses hepatocellular carcinoma progression by inhibiting CUL4A-mediated ubiquitination of LATS1. J Hematol Oncol 10(1):91–91
Nielsen EØ, Chen L, Hansen JO, Degn M, Overgaard S, Ding M (2018) Optimizing osteogenic differentiation of ovine adipose-derived stem cells by osteogenic induction medium and FGFb, BMP2, or NELL1 in vitro. Stem Cells Int 2018:9781393–9781393
Niimori-Kita K, Tamamaki N, Koizumi D, Niimori D (2018) Matrin-3 is essential for fibroblast growth factor 2-dependent maintenance of neural stem cells. Sci Rep 8(1):13412–13412
Nourissat G, Berenbaum F, Duprez D (2015) Tendon injury: from biology to tendon repair. Nat Rev Rheumatol 11:223
Poudel SB, Min C-K, Lee J-H, Shin Y-J, Kwon T-H, Jeon Y-M, Lee J-C (2019) Local supplementation with plant-derived recombinant human FGF2 protein enhances bone formation in critical-sized calvarial defects. J Bone Miner Metab
Randelli P, Conforti E, Piccoli M, Ragone V, Creo P, Cirillo F, Masuzzo P, Tringali C, Cabitza P, Tettamanti G, Gagliano N, Anastasia L (2013) Isolation and characterization of 2 new human rotator cuff and long head of biceps tendon cells possessing stem cell–like self-renewal and multipotential differentiation capacity. Am J Sports Med 41(7):1653–1664
Rui YF, Lui PPY, Wong YM, Tan Q, Chan KM (2013) Altered fate of tendon-derived stem cells isolated from a failed tendon-healing animal model of tendinopathy. Stem Cells Dev 22(7):1076–1085
Santolla FM, Vivacqua A, Lappano R, Rigiracciolo CD, Cirillo F, Galli RG, Talia M, Brunetti G, Miglietta MA, Belfiore A et al (2019) GPER mediates a feedforward FGF2/FGFR1 paracrine activation coupling CAFs to cancer cells toward breast tumor progression. Cells 8(3)
Taniue K, Kurimoto A, Sugimasa H, Nasu E, Takeda Y, Iwasaki K, Nagashima T, Okada-Hatakeyama M, Oyama M, Kozuka-Hata H, Hiyoshi M, Kitayama J, Negishi L, Kawasaki Y, Akiyama T (2016) Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF1. Proc Natl Acad Sci U S A 113(5):1273–1278
Thomopoulos S, Parks WC, Rifkin DB, Derwin KA (2015) Mechanisms of tendon injury and repair. J Orthop Res 33(6):832–839
Tokunaga T, Shukunami C, Okamoto N, Taniwaki T, Oka K, Sakamoto H, Ide J, Mizuta H, Hiraki Y (2015) FGF-2 stimulates the growth of tenogenic progenitor cells to facilitate the generation of tenomodulin-positive tenocytes in a rat rotator cuff healing model. Am J Sports Med 43(10):2411–2422
Viganò M, Perucca Orfei C, Colombini A, Stanco D, Randelli P, Sansone V, de Girolamo L (2017) Different culture conditions affect the growth of human tendon stem/progenitor cells (TSPCs) within a mixed tendon cells (TCs) population. J Exp Orthop 4(1):8–8
Wang JHC, Nirmala X (2016) Application of tendon stem/progenitor cells and platelet-rich plasma to treat tendon injuries. Oper Tech Orthop 26(2):68–72
Wu R, Ruan J, Sun Y, Liu M, Sha Z, Fan C, Wu Q (2018) Long non-coding RNA HIF1A-AS2 facilitates adipose-derived stem cells (ASCs) osteogenic differentiation through miR-665/IL6 axis via PI3K/Akt signaling pathway. Stem Cell Res Ther 9(1):348–348
Yang Liu BW (2018) Knockdown of long non-coding RNA TUG1 suppresses osteoblast apoptosis in particle-induced osteolysis by up-regulating BMP-7. Clin Surg Res Commun 2(4):19–25
Yi J, Liu D, Xiao J (2019) LncRNA MALAT1 sponges miR-30 to promote osteoblast differentiation of adipose-derived mesenchymal stem cells by promotion of Runx2 expression. Cell Tissue Res 376(1):113–121
Yoon J-H, Abdelmohsen K, Kim J, Yang X, Martindale JL, Tominaga-Yamanaka K, White EJ, Orjalo AV, Rinn JL, Kreft SG et al (2013) Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination. Nat Commun 4:2939–2939
Yu C, Liu F, Xie F, Dong N, Guo S, Wang Y, Li L (2017) LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification. Cardiovasc Res 114(1):168–179
Yu Y, Chen Y, Zhang X, Lu X, Hong J, Guo X, Zhou D (2018) Knockdown of lncRNA KCNQ1OT1 suppresses the adipogenic and osteogenic differentiation of tendon stem cell via downregulating miR-138 target genes PPARγ and RUNX2. Cell Cycle 17(19–20):2374–2385
Zhang C, Li Q, Deng S, Fu W, Tang X, Chen G, Qin T, Li J (2016) bFGF- and CaPP-loaded fibrin clots enhance the bioactivity of the tendon-bone Interface to augment healing. Am J Sports Med 44(8):1972–1982
Zhang G-W, Gu T-X, Guan X-Y, Sun X-J, Qi X, Li X-Y, Wang X-B, Yu L, Jiang D-Q, Tang R, Li-Ling J (2015a) bFGF binding cardiac extracellular matrix promotes the repair potential of bone marrow mesenchymal stem cells in a rabbit model for acute myocardial infarction. Biomed Mater 10(6):065018
Zhang H-Y, Wang Z-G, Wu F-Z, Kong X-X, Yang J, Lin B-B, Zhu S-P, Lin L, Gan C-S, Fu X-B, Li XK, Xu HZ, Xiao J (2013) Regulation of autophagy and ubiquitinated protein accumulation by bFGF promotes functional recovery and neural protection in a rat model of spinal cord injury. Mol Neurobiol 48(3):452–464
Zhang J, Wang JHC (2010) Platelet-rich plasma releasate promotes differentiation of tendon stem cells into active tenocytes. Am J Sports Med 38(12):2477–2486
Zhang Q, Ge h, Jiang Y, Cheng B, Zhou D, Xu N (2015b) Microarray profiling analysis of long non-coding RNAs expression in tendinopathy: identification for potential biomarkers and mechanisms. Int J Exp Pathol 96(6):387–394
Zhao J, Du P, Cui P, Qin Y, Hu C, Wu J, Zhou Z, Zhang W, Qin L, Huang G (2018) LncRNA PVT1 promotes angiogenesis via activating the STAT3/VEGFA axis in gastric cancer. Oncogene 37(30):4094–4109
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This study was supported by fund of the Zhejiang Provincial Natural Science Foundation (No.Y18H060051), Zhejiang Medical and Health Science and Technology Project (No. 2019RC218), and Wenzhou Municipal Science and Technology Bureau (No. Y20190077).
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Editor: Tetsuji Okamoto
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Yu, Y., Chen, Y., Zheng, Yj. et al. LncRNA TUG1 promoted osteogenic differentiation through promoting bFGF ubiquitination. In Vitro Cell.Dev.Biol.-Animal 56, 42–48 (2020). https://doi.org/10.1007/s11626-019-00410-y
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DOI: https://doi.org/10.1007/s11626-019-00410-y