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01-03-2019 | Original Article

MicroRNA-92a-1-5p influences osteogenic differentiation of MC3T3-E1 cells by regulating β-catenin

Authors: Zhiping Lin, Yangyang Tang, Hongchang Tan, Daozhang Cai

Published in: Journal of Bone and Mineral Metabolism | Issue 2/2019

Abstract

Osteoblastic differentiation is a complex process that is critical for proper bone formation. An increasing number of studies have suggested that microRNAs (miRNAs) are pivotal regulators in various physiological and pathological processes, including osteogenesis. Here, we discuss the influence of miRNA-92a-1-5p on osteogenic differentiation. We found that miR-92a-1-5p was obviously downregulated during osteogenic differentiation of MC3T3-E1 cells. Gain-of-function and loss-of-function experiments revealed that miR-92a-1-5p was a negative regulator of osteogenic differentiation. Experimental validation demonstrated that β-catenin, which acts as a positive regulator of osteogenic differentiation, was negatively regulated by miR-92a1-5p. The findings of this study provide new insights into the possibility of miR-92a1-5p being a potential therapeutic target in the management of bone regeneration-related diseases.

Zhang J, Guan J, Qi X, Ding H, Yuan H, Xie Z, Chen C, Li X, Zhang C, Huang Y (2016) Dimethyloxaloylglycine promotes the angiogenic activity of mesenchymal stem cells derived from iPSCs via activation of the PI3K/Akt pathway for bone regeneration. Int J Biol Sci 12:639–652. https://doi.org/10.7150/ijbs.14025 CrossRefPubMedPubMedCentral

Ortega-Oller I, Padial-Molina M, Galindo-Moreno P, O’Valle F, Jodar-Reyes AB, Peula-Garcia JM (2015) Bone regeneration from PLGA micro-nanoparticles. Biomed Res Int 2015:415289. https://doi.org/10.1155/2015/415289 CrossRefPubMedPubMedCentral

Serrano J, Romo E, Bermudez M, Narayanan AS, Zeichner-David M, Santos L, Arzate H (2013) Bone regeneration in rat cranium critical-size defects induced by Cementum Protein 1 (CEMP1). PLoS One 8:e78807. https://doi.org/10.1371/journal.pone.0078807 CrossRefPubMedPubMedCentral

Thor A, Palmquist A, Hirsch JM, Rannar LE, Derand P, Omar O (2016) Clinical, morphological, and molecular evaluations of bone regeneration with an additive manufactured osteosynthesis plate. J Craniofacial Surg 27:1899–1904. https://doi.org/10.1097/SCS.0000000000002939 CrossRef

D’Mello S, Atluri K, Geary SM, Hong L, Elangovan S, Salem AK (2017) Bone regeneration using gene-activated matrices. AAPS J 19:43–53. https://doi.org/10.1208/s12248-016-9982-2 CrossRefPubMed

Liu X, McKenzie JA, Maschhoff CW, Gardner MJ, Silva MJ (2017) Exogenous hedgehog antagonist delays but does not prevent fracture healing in young mice. Bone 103:241–251. https://doi.org/10.1016/j.bone.2017.07.017 CrossRefPubMedPubMedCentral

Wang Y, Newman MR, Ackun-Farmmer M, Baranello MP, Sheu TJ, Puzas JE, Benoit DSW (2017) Fracture-targeted delivery of beta-catenin agonists via peptide-functionalized nanoparticles augments fracture healing. ACS Nano 11:9445–9458. https://doi.org/10.1021/acsnano.7b05103 CrossRefPubMedPubMedCentral

Wang J, He M, Wang G, Fu Q (2017) Organic gallium treatment improves osteoporotic fracture healing through affecting the OPG/RANKL ratio and expression of serum inflammatory cytokines in ovariectomized rats. Biol Trace Elem Res. https://doi.org/10.1007/s12011-017-1123-y CrossRefPubMedPubMedCentral

Simpson A (2017) The forgotten phase of fracture healing: the need to predict nonunion. Bone Joint Res 6:610–611. https://doi.org/10.1302/2046-3758.610.BJR-2017-0301 CrossRefPubMedPubMedCentral

10.

Bushati N, Cohen SM (2007) microRNA functions. Annu Rev Cell Dev Biol 23:175–205. https://doi.org/10.1146/annurev.cellbio.23.090506.123406 CrossRefPubMed

11.

Henshall DC (2014) MicroRNA and epilepsy: profiling, functions and potential clinical applications. Curr Opin Neurol 27:199–205. https://doi.org/10.1097/WCO.0000000000000079 CrossRefPubMedPubMedCentral

12.

Foshay KM, Gallicano GI (2007) Small RNAs, big potential: the role of MicroRNAs in stem cell function. Curr Stem Cell Res Ther 2:264–271CrossRefPubMed

13.

Hobert O (2008) Gene regulation by transcription factors and microRNAs. Science 319:1785–1786. https://doi.org/10.1126/science.1151651 CrossRefPubMed

14.

Taipaleenmaki H, Bjerre Hokland L, Chen L, Kauppinen S, Kassem M (2012) Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation. Eur J Endocrinol 166:359–371. https://doi.org/10.1530/EJE-11-0646 CrossRefPubMed

15.

Chen L, Holmstrom K, Qiu W, Ditzel N, Shi K, Hokland L, Kassem M (2014) MicroRNA-34a inhibits osteoblast differentiation and in vivo bone formation of human stromal stem cells. Stem Cells 32:902–912. https://doi.org/10.1002/stem.1615 CrossRefPubMed

16.

Bae Y, Yang T, Zeng HC, Campeau PM, Chen Y, Bertin T, Dawson BC, Munivez E, Tao J, Lee BH (2012) miRNA-34c regulates Notch signaling during bone development. Hum Mol Genet 21:2991–3000. https://doi.org/10.1093/hmg/dds129 CrossRefPubMedPubMedCentral

17.

Jia J, Tian Q, Ling S, Liu Y, Yang S, Shao Z (2013) miR-145 suppresses osteogenic differentiation by targeting Sp7. FEBS Lett 587:3027–3031. https://doi.org/10.1016/j.febslet.2013.07.030 CrossRefPubMed

18.

Fukuda T, Ochi H, Sunamura S, Haiden A, Bando W, Inose H, Okawa A, Asou Y, Takeda S (2015) MicroRNA-145 regulates osteoblastic differentiation by targeting the transcription factor Cbfb. FEBS Lett 589:3302–3308. https://doi.org/10.1016/j.febslet.2015.09.024 CrossRefPubMed

19.

Wang H, Cui Y, Luan J, Zhou X, Li C, Li H, Shi L, Han J (2017) MiR-5100 promotes osteogenic differentiation by targeting Tob2. J Bone Miner Metab 35:608–615. https://doi.org/10.1007/s00774-016-0799-y CrossRefPubMed

20.

Vishal M, Vimalraj S, Ajeetha R, Gokulnath M, Keerthana R, He Z, Partridge NC, Selvamurugan N (2017) MicroRNA-590-5p stabilizes Runx2 by targeting Smad7 during osteoblast differentiation. J Cell Physiol 232:371–380. https://doi.org/10.1002/jcp.25434 CrossRefPubMed

21.

Seeliger C, Karpinski K, Haug AT, Vester H, Schmitt A, Bauer JS, van Griensven M (2014) Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures. J Bone Miner Res 29:1718–1728. https://doi.org/10.1002/jbmr.2175 CrossRefPubMed

22.

Lai L, Song Y, Liu Y, Chen Q, Han Q, Chen W, Pan T, Zhang Y, Cao X, Wang Q (2013) MicroRNA-92a negatively regulates Toll-like receptor (TLR)-triggered inflammatory response in macrophages by targeting MKK4 kinase. J Biol Chem 288:7956–7967. https://doi.org/10.1074/jbc.M112.445429 CrossRefPubMedPubMedCentral

23.

Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, Chavakis E, Potente M, Tjwa M, Urbich C, Zeiher AM, Dimmeler S (2009) MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324:1710–1713. https://doi.org/10.1126/science.1174381 CrossRefPubMed

24.

Liu Y, Liu W, Hu C, Xue Z, Wang G, Ding B, Luo H, Tang L, Kong X, Chen X, Liu N, Ding Y, Jin Y (2011) MiR-17 modulates osteogenic differentiation through a coherent feed-forward loop in mesenchymal stem cells isolated from periodontal ligaments of patients with periodontitis. Stem Cells 29:1804–1816. https://doi.org/10.1002/stem.728 CrossRefPubMed

25.

Zhou M, Ma J, Chen S, Chen X, Yu X (2014) MicroRNA-17-92 cluster regulates osteoblast proliferation and differentiation. Endocrine 45:302–310. https://doi.org/10.1007/s12020-013-9986-y CrossRefPubMed

26.

Notomi T, Kuno M, Hiyama A, Nozaki T, Ohura K, Ezura Y, Noda M (2017) Role of lysosomal channel protein TPC2 in osteoclast differentiation and bone remodeling under normal and low-magnesium conditions. J Biol Chem 292:20998–21010. https://doi.org/10.1074/jbc.M117.780072 CrossRefPubMedPubMedCentral

27.

Hasegawa T, Amizuka N (2017) Bone remodeling and modeling/mini-modeling. Clin Calcium 27:1713–1722PubMed

28.

Jimi E (2017) The role of osteoclastic bone resorption on bone remodeling. Clin Calcium 27:1689–1695PubMed

29.

Wang N, Xue P, Wu X, Ma J, Wang Y, Li Y (2018) Role of sclerostin and dkk1 in bone remodeling in type 2 diabetic patients. Endocr Res 43:29–38. https://doi.org/10.1080/07435800.2017.1373662 CrossRefPubMed

30.

Yamamoto N (2017) Basic concept of bone remodeling. Clin Calcium 27:1683–1688PubMed

31.

Inoue D (2017) Regulation of bone remodeling by anti-resorptives. Clin Calcium 27:1775–1783PubMed

32.

Beck GR Jr, Moran E, Knecht N (2003) Inorganic phosphate regulates multiple genes during osteoblast differentiation, including Nrf2. Exp Cell Res 288:288–300CrossRefPubMed

33.

Pico MJ, Hashemi S, Xu F, Nguyen KH, Donnelly R, Moran E, Flowers S (2016) Glucocorticoid receptor-mediated cis-repression of osteogenic genes requires BRM-SWI/SNF. Bone Rep 5:222–227. https://doi.org/10.1016/j.bonr.2016.07.006 CrossRefPubMedPubMedCentral

34.

Swinehart IT, Schlientz AJ, Quintanilla CA, Mortlock DP, Wellik DM (2013) Hox11 genes are required for regional patterning and integration of muscle, tendon and bone. Development 140:4574–4582. https://doi.org/10.1242/dev.096693 CrossRefPubMedPubMedCentral

35.

Marini F, Cianferotti L, Brandi ML (2016) Epigenetic mechanisms in bone biology and osteoporosis: can they drive therapeutic choices? Int J Mol Sci. https://doi.org/10.3390/ijms17081329 CrossRefPubMedPubMedCentral

36.

Komori T (2016) Glucocorticoid signaling and bone biology. Horm Metab Res 48:755–763. https://doi.org/10.1055/s-0042-110571 CrossRefPubMed

37.

Del Carpio-Cano FE, Dela Cadena RA, Sawaya BE (2013) HIV and bone disease: a perspective of the role of microRNAs in bone biology upon HIV infection. J Osteoporos 2013:571418. https://doi.org/10.1155/2013/571418 CrossRefPubMedPubMedCentral

38.

Guerrero J, Oliveira H, Aid R, Bareille R, Siadous R, Letourneur D, Mao Y, Kohn J, Amedee J (2017) Influence of the three-dimensional culture of human bone marrow mesenchymal stromal cells within a macroporous polysaccharides scaffold on Pannexin 1 and Pannexin 3. J Tissue Eng Regen Med. https://doi.org/10.1002/term.2625 CrossRef

39.

Xu SJ, Qiu ZY, Wu JJ, Kong XD, Weng XS, Cui FZ, Wang XM (2016) Osteogenic differentiation gene expression profiling of hMSCs on hydroxyapatite and mineralized collagen. Tissue Eng Part A 22:170–181. https://doi.org/10.1089/ten.TEA.2015.0237 CrossRefPubMed

40.

Rawadi G, Vayssiere B, Dunn F, Baron R, Roman-Roman S (2003) BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a Wnt autocrine loop. J Bone Miner Res 18:1842–1853. https://doi.org/10.1359/jbmr.2003.18.10.1842 CrossRefPubMed

41.

Tang N, Song WX, Luo J, Luo X, Chen J et al (2009) BMP-9-induced osteogenic differentiation of mesenchymal progenitors requires functional canonical Wnt/beta-catenin signalling. J Cell Mol Med 13:2448–2464. https://doi.org/10.1111/j.1582-4934.2008.00569.x CrossRefPubMed

42.

Zhang R, Oyajobi BO, Harris SE, Chen D, Tsao C, Deng HW, Zhao M (2013) Wnt/beta-catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts. Bone 52:145–156. https://doi.org/10.1016/j.bone.2012.09.029 CrossRefPubMed

43.

Huang C, Ogawa R (2010) Mechanotransduction in bone repair and regeneration. FASEB J 24:3625–3632. https://doi.org/10.1096/fj.10-157370 CrossRefPubMed

44.

Ghadakzadeh S, Kannu P, Whetstone H, Howard A, Alman BA (2016) beta-Catenin modulation in neurofibromatosis type 1 bone repair: therapeutic implications. FASEB J 30:3227–3237. https://doi.org/10.1096/fj.201500190RR CrossRefPubMed

45.

Baht GS, Silkstone D, Vi L, Nadesan P, Amani Y, Whetstone H, Wei Q, Alman BA (2015) Exposure to a youthful circulation rejuvenates bone repair through modulation of beta-catenin. Nat Commun 6:7131. https://doi.org/10.1038/ncomms8131 CrossRefPubMed

46.

Minear S, Leucht P, Miller S, Helms JA (2010) rBMP represses Wnt signaling and influences skeletal progenitor cell fate specification during bone repair. J Bone Miner Res 25:1196–1207. https://doi.org/10.1002/jbmr.29 CrossRefPubMedPubMedCentral

47.

Shi GX, Zheng XF, Zhu C, Li B, Wang YR, Jiang SD, Jiang LS (2017) Evidence of the role of R-spondin 1 and its receptor Lgr4 in the transmission of mechanical stimuli to biological signals for bone formation. Int J Mol Sci. https://doi.org/10.3390/ijms18030564 CrossRefPubMedPubMedCentral

48.

Leucht P, Helms JA (2015) Wnt signaling: an emerging target for bone regeneration. J Am Acad Orthop Surg 23:67–68. https://doi.org/10.5435/JAAOS-23-01-67 CrossRefPubMed

Title: MicroRNA-92a-1-5p influences osteogenic differentiation of MC3T3-E1 cells by regulating β-catenin
Authors: Zhiping Lin
Yangyang Tang
Hongchang Tan
Daozhang Cai
Publication date: 01-03-2019
Publisher: Springer Japan
Published in: Journal of Bone and Mineral Metabolism / Issue 2/2019
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-018-0935-y

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