miR-1307-3p suppresses the chondrogenic differentiation of human adipose-derived stem cells by targeting BMPR2

Yang,Zhen; Li,Rui; Ao,Jun; Wa,Qing‑De; Zhang,Yi; Chen,Long; Wen,Jing; Chen,Biao; Pan,Wei; Li,Bo; Tian,Xiao‑Bin

doi:10.3892/ijmm.2018.3891

miR-1307-3p suppresses the chondrogenic differentiation of human adipose-derived stem cells by targeting BMPR2

Authors:
- Zhen Yang
- Rui Li
- Jun Ao
- Qing‑De Wa
- Yi Zhang
- Long Chen
- Jing Wen
- Biao Chen
- Wei Pan
- Bo Li
- Xiao‑Bin Tian
View Affiliations

Affiliations: Medical College of Guizhou University, Guiyang, Guizhou 550025, P.R. China, Guizhou Provincial People's Hospital (People's Hospital of Guizhou University), Guiyang, Guizhou 550002, P.R. China, Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
Published online on: September 21, 2018 https://doi.org/10.3892/ijmm.2018.3891
Pages: 3115-3124
Copyright: © Yang 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

MicroRNAs (miRs) are involved in several physiological processes, including chondrogenic differentiation, however, their expression and roles in the chondrogenic differentiation of human adipose‑derived stem cells (hADSCs) remain to be fully elucidated to date. Our previous study showed that miR‑1307‑3p was significantly downregulated during chondrogenic differentiation by microarray and northern blot analysis. The present study aimed to investigate the effects of miR‑1307‑3p on chondrogenic differentiation and the underlying mechanisms. First, the decreased expression of miR‑1307‑3p was confirmed by reverse transcription‑quantitative polymerase chain reaction analysis. Subsequently, gain‑ and loss‑of‑function of miR‑1307‑3p experiments showed that the overexpression of miR‑1307‑3p suppressed the deposition of cartilage matrix proteoglycans and decreased the expression of cartilage‑related markers, including sex determining region Y‑box 9, collagen type II α1 chain and aggrecan, whereas the knockdown of miR‑1307‑3p had the opposite effect. In addition, bone morphogenetic protein receptor type 2 (BMPR2) was identified as a target of miR‑1307‑3p. Further mechanistic investigations showed that miR‑1307‑3p attenuated the chondrogenic differentiation of hADSCs at least partly by inhibiting BMPR2‑mothers against decapentaplegic signaling pathways. In conclusion, the findings revealed that miR‑1307‑3p inhibited the chondrogenic differentiation of hADSCs by targeting BMPR2 and its downstream signaling pathway, which may provide novel therapeutic clues for the treatment of cartilage injury.

View Figures

View References

1	Ge Z, Hu Y, Heng BC, Yang Z, Ouyang H, Lee EH and Cao T: Osteoarthritis and therapy. Arthritis Rheum. 55:493–500. 2006. View Article : Google Scholar : PubMed/NCBI
2	Zhang J and Chen J: Bone tissue regeneration-Application of mesenchymal stem cells and cellular and molecular mechanisms. Curr Stem Cell Res Ther. 12:357–364. 2017. View Article : Google Scholar
3	Vallée M, Côté JF and Fradette J: Adipose-tissue engineering: Taking advantage of the properties of human adipose-derived stem/stromal cells. Pathol Biol (Paris). 57:309–317. 2009. View Article : Google Scholar
4	Wang S, Qu X and Zhao RC: Mesenchymal stem cells hold promise for regenerative medicine. Front Med. 5:372–378. 2011. View Article : Google Scholar : PubMed/NCBI
5	Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P and Hedrick MH: Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 13:4279–4295. 2002. View Article : Google Scholar : PubMed/NCBI
6	Gimble J and Guilak F: Adipose-derived adult stem cells: Isolation, characterization, and differentiation potential. Cytotherapy. 5:362–369. 2003. View Article : Google Scholar : PubMed/NCBI
7	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
8	Dong H, Lei J, Ding L, Wen Y, Ju H and Zhang X: MicroRNA: Function, detection, and bioanalysis. Chem Rev. 113:6207–6233. 2013. View Article : Google Scholar : PubMed/NCBI
9	Wu C, Tian B, Qu X, Liu F, Tang T, Qin A, Zhu Z and Dai K: MicroRNAs play a role in chondrogenesis and osteoarthritis (Review). Int J Mol Med Jul. 34:13–23. 2014. View Article : Google Scholar
10	Lee S, Yoon DS, Paik S, Lee KM, Jang Y and Lee JW: microRNA-495 inhibits chondrogenic differentiation in human mesenchymal stem cells by targeting Sox9. Stem Cells Dev. 23:1798–1808. 2014. View Article : Google Scholar : PubMed/NCBI
11	Zhang Y, Huang X and Yuan Y: MicroRNA-410 promotes chondrogenic differentiation of human bone marrow mesenchymal stem cells through downregulating Wnt3a. Am J Transl Res. 9:136–145. 2017.
12	Zhang Z, Kang Y, Zhang Z, Zhang H, Duan X, Liu J, Li X and Liao W: Expression of microRNAs during chondrogenesis of human adipose-derived stem cells. Osteoarthritis Cartilage. 20:1638–1646. 2012. View Article : Google Scholar : PubMed/NCBI
13	Yang Z, Hao J and Hu ZM: MicroRNA expression profiles in human adipose-derived stem cells during chondrogenic differentiation. Int J Mol Med. 35:579–586. 2015. View Article : Google Scholar :
14	Hou C, Yang Z, Kang Y, Zhang Z, Fu M, He A, Zhang Z and Liao W: MiR-193b regulates early chondrogenesis by inhibiting the TGF-beta2 signaling pathway. FEBS Lett. 589:1040–1047. 2015. View Article : Google Scholar : PubMed/NCBI
15	Hou C, Zhang Z, Zhang Z, Wu P, Zhao X, Fu M, Sheng P, Kang Y and Liao W: Presence and function of microRNA-92a in chondrogenic ATDC5 and adipose-derived mesenchymal stem cells. Mol Med Rep. 12:4877–4886. 2015. View Article : Google Scholar : PubMed/NCBI
16	Xu J, Kang Y, Liao WM and Yu L: MiR-194 regulates chondrogenic differentiation of human adipose-derived stem cells by targeting Sox5. PLoS One. 7:e318612012. View Article : Google Scholar : PubMed/NCBI
17	Wu SC, Hsiao HF, Ho ML, Hung YL, Chang JK, Wang GJ and Wang CZ: Suppression of discoidin domain receptor 1 expression enhances the chondrogenesis of adipose-derived stem cells. Am J Physiol Cell Physiol. 308:C685–C896. 2015. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar
19	Johnson JJ, Loeffert AC, Stokes J, Olympia RP, Bramley H and Hicks SD: Association of salivary microRNA changes with prolonged concussion symptoms. JAMA Pediatr. 172:65–73. 2018. View Article : Google Scholar
20	Chen Q, Mao Y, Meng F, Wang L, Zhang H, Wang W and Hua D: Rs7911488 modified the efficacy of capecitabine-based therapy in colon cancer through altering miR-1307p and TYMS expression. Oncotarget. 8:74312–74319. 2017.PubMed/NCBI
21	García-Donas J, Beuselinck B, Inglada-Pérez L, Graña O, Schöffski P, Wozniak A, Bechter O, Apellániz-Ruiz M, Leandro-García LJ, Esteban E, et al: Deep sequencing reveals microRNAs predictive of antiangiogenic drug response. JCI Insight. 1:e860512016. View Article : Google Scholar : PubMed/NCBI
22	Shimomura A, Shiino S, Kawauchi J, Takizawa S, Sakamoto H, Matsuzaki J, Ono M, Takeshita F, Niida S, Shimizu C, et al: Novel combination of serum microRNA for detecting breast cancer in the early stage. Cancer Sci. 107:326–334. 2016. View Article : Google Scholar : PubMed/NCBI
23	Kang Q, Song WX, Luo Q, Tang N, Luo J, Luo X, Chen J, Bi Y, He BC, Park JK, et al: A comprehensive analysis of the dual roles of BMPs in regulating adipogenic andosteogenic differentiation of mesenchymal progenitor cells. Stem Cells Dev. 18:545–559. 2009. View Article : Google Scholar
24	Zhou X, Wang J, Sun H, Qi Y, Xu W, Luo D, Jin X, Li C, Chen W, Lin Z, et al: MicroRNA-99a regulates early chondrogenic differentiation of rat mesenchymal stem cells by targeting the BMPR2 gene. Cell Tissue Res. 366:143–53. 2016. View Article : Google Scholar : PubMed/NCBI
25	Cao Y, LV Q and LV C: MicroRNA-153 suppresses the osteogenic differentiation of human mesenchymal stem cells by targeting bone morphogenetic protein receptor type II. Int J Mol Med. 36:760–766. 2015. View Article : Google Scholar : PubMed/NCBI
26	Zeng Y, Qu X, Li H, Huang S, Wang S, Xu Q, Lin R, Han Q, Li J and Zhao RC: MicroRNA-100 regulates osteogenic differentiation of human adipose-derived mesenchymal stem cells by targeting BMPR2. FEBS Lett. 586:2375–2381. 2012. View Article : Google Scholar : PubMed/NCBI
27	Liu F, Ventura F, Doody J and Massagué J: Human type II receptor for bone morphogenic proteins (BMPs): Extension of the two-kinase receptor model to the BMPs. Mol Cell Bio. 15:3479–3486. 1995. View Article : Google Scholar
28	Miyazono K, Maeda S and Imamura T: BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev. 16:251–263. 2005. View Article : Google Scholar : PubMed/NCBI