Inhibition of microRNA‑34a ameliorates murine collagen‑induced arthritis

Dang,Qiujie; Yang,Fan; Lei,Hongwei; Liu,Xin; Yan,Minglu; Huang,He; Fan,Xuemei; Li,Yang

doi:10.3892/etm.2017.4708

Inhibition of microRNA‑34a ameliorates murine collagen‑induced arthritis

Authors:
- Qiujie Dang
- Fan Yang
- Hongwei Lei
- Xin Liu
- Minglu Yan
- He Huang
- Xuemei Fan
- Yang Li
View Affiliations

Affiliations: Department of Rheumatology and Immunology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: June 28, 2017 https://doi.org/10.3892/etm.2017.4708
Pages: 1633-1639
Copyright: © Dang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

Rheumatoid arthritis (RA) is one of the most frequently occurring autoimmne diseases, with symptoms including synovium hyperplasia, immune disorder, cartilage damage and bone resorption. It has previously been demonstrated that microRNA‑34a (miR‑34a) may participate in cell apoptosis, immune activation and bone metabolism, therefore the present study investigated the effects of miR‑34a on RA. Collagen‑induced arthritic (CIA) mice were employed as a murine model of experimental arthritis, and it was demonstrated that the level of miR‑34a in the spleens, lymph nodes and synovium was increased in the CIA mice compared with normal DBA/1j mice. Administration of miR‑34a antagomir, the chemically modified inhibitor, ameliorated CIA and delayed the onset of symptoms. Arthritis scores decreased and joint swelling was alleviated with the miR‑34a antagomir treatment and the expression of inflammatory cytokines was decreased. miR‑34a antagomir delivery significantly decreased the percentage of T cells present including T helper (Th) 1, Th2, Th17 and regulatory T cells. Furthermore miR‑34a antagomir‑treated CIA mice demonstrated decreased inflammatory‑induced bone loss. Overall, it was observed that inhibition of miR‑34a ameliorated murine arthritis, downregulated T cell percentage and cytokine expression, and suppressed bone loss. The experimental results suggest that inhibition of miR‑34a may offer a novel alternative for the treatment of RA.

View Figures

View References

1	Alamanos Y, Voulgari PV and Drosos AA: Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: A systematic review. Semin Arthritis Rheum. 36:182–188. 2006. View Article : Google Scholar : PubMed/NCBI
2	Goronzy JJ and Weyand CM: T-cell regulation in rheumatoid arthritis. Curr Opin Rheumatol. 16:212–217. 2004. View Article : Google Scholar : PubMed/NCBI
3	Leipe J, Grunke M, Dechant C, Reindl C, Kerzendorf U, Schulze-Koops H and Skapenko A: Role of Th17 cells in human autoimmune arthritis. Arthritis Rheum. 62:2876–2885. 2010. View Article : Google Scholar : PubMed/NCBI
4	Smolen JS and Aletaha D: Rheumatoid arthritis therapy reappraisal: Strategies, opportunities and challenges. Nat Rev Rheumatol. 11:276–289. 2015. View Article : Google Scholar : PubMed/NCBI
5	Stoffer MA, Schoels MM, Smolen JS, Aletaha D, Breedveld FC, Burmester G, Bykerk V, Dougados M, Emery P, Haraoui B, et al: Evidence for treating rheumatoid arthritis to target: Results of a systematic literature search update. Ann Rheum Dis. 75:16–22. 2016. View Article : Google Scholar : PubMed/NCBI
6	Xiao C and Rajewsky K: MicroRNA control in the immune system: Basic principles. Cell. 136:26–36. 2009. View Article : Google Scholar : PubMed/NCBI
7	Gonzalez-Martin A, Adams BD, Lai M, Shepherd J, Salvador-Bernaldez M, Salvador JM, Lu J, Nemazee D and Xiao C: The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity. Nat Immunol. 17:433–440. 2016. View Article : Google Scholar : PubMed/NCBI
8	O'Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA, Kahn ME, Rao DS and Baltimore D: MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity. 33:607–619. 2010. View Article : Google Scholar : PubMed/NCBI
9	Jiang P, Liu R, Zheng Y, Liu X, Chang L, Xiong S and Chu Y: MiR-34a inhibits lipopolysaccharide-induced inflammatory response through targeting Notch1 in murine macrophages. Exp Cell Res. 318:1175–1184. 2012. View Article : Google Scholar : PubMed/NCBI
10	Shin J, Xie D and Zhong XP: MicroRNA-34a enhances T cell activation by targeting diacylglycerol kinase ζ. PLoS One. 8:e779832013. View Article : Google Scholar : PubMed/NCBI
11	Junker A, Krumbholz M, Eisele S, Mohan H, Augstein F, Bittner R, Lassmann H, Wekerle H, Hohlfeld R and Meinl E: MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain. 132:3342–3352. 2009. View Article : Google Scholar : PubMed/NCBI
12	Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, Dong Q, Pang Z, Guan Q, Gao L, et al: Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: A clinical study. Acta Diabetol. 48:61–69. 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	Kim D, Song J, Kim S, Park HM, Chun CH, Sonn J and Jin EJ: MicroRNA-34a modulates cytoskeletal dynamics through regulating RhoA/Rac1 cross-talk in chondroblasts. J Biol Chem. 287:12501–12509. 2012. View Article : Google Scholar : PubMed/NCBI
15	Kumar B, Yadav A, Lang J, Teknos TN and Kumar P: Dysregulation of microRNA-34a expression in head and neck squamous cell carcinoma promotes tumor growth and tumor angiogenesis. PLoS One. 7:e376012012. View Article : Google Scholar : PubMed/NCBI
16	Yoshida Y, Ogata A, Kang S, Ebina K, Shi K, Nojima S, Kimura T, Ito D, Morimoto K, Nishide M, et al: Semaphorin 4D contributes to rheumatoid arthritis by inducing inflammatory cytokine production: Pathogenic and therapeutic implications. Arthritis Rheumatol. 67:1481–1490. 2015. View Article : Google Scholar : PubMed/NCBI
17	Schett G and Teitelbaum SL: Osteoclasts and arthritis. J Bone Miner Res. 24:1142–1146. 2009. View Article : Google Scholar
18	Lim HW, Kang SG, Ryu JK, Schilling B, Fei M, Lee IS, Kehasse A, Shirakawa K, Yokoyama M, Schnölzer M, et al: SIRT1 deacetylates RORγt and enhances Th17 cell generation. J Exp Med. 212:607–617. 2015. View Article : Google Scholar : PubMed/NCBI
19	Wang H, Geng J, Wen X, Bi E, Kossenkov AV, Wolf AI, Tas J, Choi YS, Takata H, Day TJ, et al: The transcription factor Foxp1 is a critical negative regulator of the differentiation of follicular helper T cells. Nat Immunol. 15:667–675. 2014. View Article : Google Scholar : PubMed/NCBI
20	McInnes IB and Schett G: The pathogenesis of rheumatoid arthritis. N Engl J Med. 365:2205–2219. 2011. View Article : Google Scholar : PubMed/NCBI