Validation of downregulated microRNAs during osteoclast formation and osteoporosis progression

Ma,Yan; Shan,Zhi; Ma,Jianjun; Wang,Qiang; Chu,Junjie; Xu,Peiwei; Qin,An; Fan,Shunwu

doi:10.3892/mmr.2016.4765

Validation of downregulated microRNAs during osteoclast formation and osteoporosis progression

Authors:
- Yan Ma
- Zhi Shan
- Jianjun Ma
- Qiang Wang
- Junjie Chu
- Peiwei Xu
- An Qin
- Shunwu Fan
View Affiliations

Affiliations: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China, Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China
Published online on: January 12, 2016 https://doi.org/10.3892/mmr.2016.4765
Pages: 2273-2280

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Enhanced osteoclast formation and function have essential roles during post‑menopausal osteoporosis. A number of cytokines have been reported to regulate osteoclastogenesis and to be involved during the pathogenesis of osteoporosis. However, the regulation of osteolysis by microRNAs (miRNAs) has remained to be fully elucidated. The present study used a microarray analysis to identify a variety of miRNAs that are differentially expressed during osteoclast formation. Six down‑regulated miRNAs, miR‑21a‑5p, miR‑27a‑3p, let‑7i‑5p, miR‑22‑3p, miR‑340‑5p and miR‑23a‑5p, whose molecular mechanisms during osteoclast differentiation have not been reported previously, were further assessed. Using an osteoclast formation assay and a mouse model of progressive osteoporosis, the downregulation of these miRNAs was validated in vitro and in vivo. Of note, the expression patterns of these six miRNAs were associated with the progression of osteoporosis. Therefore, these miRNAs are of potential diagnostic and therapeutic value for osteolytic diseases.

View Figures

View References

1	Rachner TD, Khosla S and Hofbauer LC: Osteoporosis: Now and the future. Lancet. 377:1276–1287. 2011. View Article : Google Scholar : PubMed/NCBI
2	Kim MS, Magno CL, Day CJ and Morrison NA: Induction of chemokines and chemokine receptors CCR2b and CCR4 in authentic human osteoclasts differentiated with RANKL and osteoclast like cells differentiated by MCP-1 and RANTES. J Cell Biochem. 97:512–518. 2006. View Article : Google Scholar
3	Matsuo K and Irie N: Osteoclastosteoblast communication. Arch Biochem Biophys. 473:201–209. 2008. View Article : Google Scholar : PubMed/NCBI
4	Dempster DW, Lambing CL, Kostenuik PJ and Grauer A: Role of RANK ligand and denosumab, a targeted RANK ligand inhibitor, in bone health and osteoporosis: A review of preclinical and clinical data. Clin Ther. 34:521–536. 2012. View Article : Google Scholar : PubMed/NCBI
5	Chong Y, Zhang J, Guo X, Li G, Zhang S, Li C, Jiao Z and Shao M: MicroRNA-503 acts as a tumor suppressor in osteosarcoma by targeting L1CAM. PLoS One. 9:e1145852014. View Article : Google Scholar : PubMed/NCBI
6	Kloos W, Vogel B and Blessing E: MiRNAs in peripheral artery disease-something gripping this way comes. Vasa. 43:163–170. 2014. View Article : Google Scholar : PubMed/NCBI
7	Schneider MR: MicroRNAs as novel players in skin development, homeostasis and disease. Br J Dermatol. 166:22–28. 2012. View Article : Google Scholar
8	Jayaswal V, Lutherborrow M, Ma DD and Yang YH: Identification of microRNA-mRNA modules using microarray data. BMC Genomics. 12:1382011. View Article : Google Scholar : PubMed/NCBI
9	Sugatani T and Hruska KA: MicroRNA-223 is a key factor in osteoclast differentiation. J Cell Biochem. 101:996–999. 2007. View Article : Google Scholar : PubMed/NCBI
10	Bluml S, Bonelli M, Niederreiter B, Puchner A, Mayr G, Hayer S, Koenders MI, van den Berg WB, Smolen J and Redlich K: Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum. 63:1281–1288. 2011. View Article : Google Scholar : PubMed/NCBI
11	Rossi M, Pitari MR, Amodio N, Di Martino MT, Conforti F, Leone E, Botta C, Paolino FM, Del Giudice T, Iuliano E, et al: miR-29b negatively regulates human osteoclastic cell differentiation and function: Implications for the treatment of multiple myeloma-related bone disease. J Cell Physiol. 228:1506–1515. 2013. View Article : Google Scholar
12	Sugatani T, Vacher J and Hruska KA: A microRNA expression signature of osteoclastogenesis. Blood. 117:3648–3657. 2011. View Article : Google Scholar : PubMed/NCBI
13	Krzeszinski JY, Wei W, Huynh H, Jin Z, Wang X, Chang TC, Xie XJ, He L, Mangala LS, Lopez-Berestein G, et al: miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2. Nature. 512:431–435. 2014. View Article : Google Scholar : PubMed/NCBI
14	Seeliger C, Karpinski K, Haug AT, Vester H, Schmitt A, Bauer JS and van Griensven M: Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures. J Bone Miner Res. 29:1718–1728. 2014. View Article : Google Scholar : PubMed/NCBI
15	Li H, Zhai Z, Liu G, Tang T, Lin Z, Zheng M, Qin A and Dai K: Sanguinarine inhibits osteoclast formation and bone resorption via suppressing RANKL-induced activation of NF-kB and ERK signaling pathways. Biochem Biophys Res Commun. 430:951–956. 2013. View Article : Google Scholar
16	Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ and Müller R: Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. 25:1468–1486. 2010. View Article : Google Scholar : PubMed/NCBI
17	Imai T, et al: Evaluation of reference genes for accurate normalization of gene expression for real time-quantitative PCR in Pyrus pyrifolia using different tissue samples and seasonal conditions. PLoS One. 9:e864922014. View Article : Google Scholar : PubMed/NCBI
18	Shibuya H, Nakasa T, Adachi N, Nagata Y, Ishikawa M, Deie M, Suzuki O and Ochi M: Overexpression of microRNA-223 in rheumatoid arthritis synovium controls osteoclast differentiation. Mod Rheumatol. 23:674–685. 2013. View Article : Google Scholar
19	Zhang J, Zhao H, Chen J, Xia B, Jin Y, Wei W, Shen J and Huang Y: Interferon-β-induced miR-155 inhibits osteoclast differentiation by targeting SOCS1 and MITF. FEBS Lett. 586:3255–3262. 2012. View Article : Google Scholar : PubMed/NCBI
20	Nakasa T, Shibuya H, Nagata Y, Niimoto T and Ochi M: The inhibitory effect of microRNA-146a expression on bone destruction in collagen-induced arthritis. Arthritis Rheum. 63:1582–1590. 2011. View Article : Google Scholar : PubMed/NCBI
21	Ell B, Mercatali L, Ibrahim T, Campbell N, Schwarzenbach H, Pantel K, Amadori D and Kang Y: Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis. Cancer Cell. 24:542–556. 2013. View Article : Google Scholar : PubMed/NCBI
22	Cheng P, Chen C, He HB, Hu R, Zhou HD, Xie H, Zhu W, Dai RC, Wu XP, Liao EY and Luo XH: miR-148a regulates osteoclastogenesis by targeting V-maf musculoaponeurotic fibrosarcoma oncogene homolog B. J Bone Miner Res. 28:1180–1190. 2013. View Article : Google Scholar
23	Lee Y, Kim HJ, Park CK, Kim YG, Lee HJ, Kim JY and Kim HH: MicroRNA-124 regulates osteoclast differentiation. Bone. 56:383–389. 2013. View Article : Google Scholar : PubMed/NCBI
24	Mizoguchi F, Murakami Y, Saito T, Miyasaka N and Kohsaka H: miR-31 controls osteoclast formation and bone resorption by targeting RhoA. Arthritis Res Ther. 15:R1022013. View Article : Google Scholar : PubMed/NCBI
25	Chen C, Cheng P, Xie H, Zhou HD, Wu XP, Liao EY and Luo XH: MiR-503 regulates osteoclastogenesis via targeting RANK. J Bone Miner Res. 29:338–347. 2014. View Article : Google Scholar
26	Guo LJ, Liao L, Yang L, Li Y and Jiang TJ: MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis. Exp Cell Res. 321:142–152. 2014. View Article : Google Scholar
27	Wu S, Huang S, Ding J, Zhao Y, Liang L, Liu T, Zhan R and He X: Multiple microRNAs modulate p21Cip1/Waf1 expression by directly targeting its 3′untranslated region. Oncogene. 29:2302–2308. 2010. View Article : Google Scholar : PubMed/NCBI
28	Park MG, Kim JS, Park SY, Lee SA, Kim HJ, Kim CS, Kim JS, Chun HS, Park JC and Kim do K: MicroRNA-27 promotes the differentiation of odontoblastic cell by targeting APC and activating Wnt/β-catenin signaling. Gene. 538:266–272. 2014. View Article : Google Scholar : PubMed/NCBI
29	Wang T and Xu Z: miR-27 promotes osteoblast differentiation by modulating Wnt signaling. Biochem Biophys Res Commun. 402:186–189. 2010. View Article : Google Scholar : PubMed/NCBI
30	Lin J, Huo R, Xiao L, Zhu X, Xie J, Sun S, He Y, Zhang J, Sun Y, Zhou Z, et al: A novel p53/microRNA-22/Cyr61 axis in synovial cells regulates inflammation in rheumatoid arthritis. Arthritis Rheumatol. 66:49–59. 2014. View Article : Google Scholar : PubMed/NCBI
31	Takata A, Otsuka M, Kojima K, Yoshikawa T, Kishikawa T, Yoshida H and Koike K: MicroRNA-22 and microRNA-140 suppress NF-kB activity by regulating the expression of NF-kB coactivators. Biochem Biophys Res Commun. 411:826–831. 2011. View Article : Google Scholar : PubMed/NCBI
32	Poenitzsch Strong AM, Setaluri V and Spiegelman VS: microRNA-340 as a modulator of RAS-RAF-MAPK signaling in melanoma. Arch Biochem Biophys. 563:118–124. 2014. View Article : Google Scholar : PubMed/NCBI