Decrease of MiR-195 Promotes Chondrocytes Proliferation and Maintenance of Chondrogenic Phenotype Via Targeting FGF-18 Pathway

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 May 5

PMID 28471382

Citations 14

Authors

Yong Wang

Tao Yang

Yadong Liu

Wei Zhao

Zhen Zhang

Ming Lu

Weiguo Zhang

Affiliations

Soon will be listed here.

Abstract

Slow growth and rapid loss of chondrogenic phenotypes are the major problems affecting chronic cartilage lesions. The role of microRNA-195 (miR-195) and its detailed working mechanism in the fore-mentioned process remains unknown. Fibroblastic growth factor 18 (FGF-18) plays a key role in cartilage homeostasis; whether miR-195 could regulate FGF-18 and its downstream signal pathway in chondrocyte proliferation and maintenance of chondrogenic phenotypes still remains unclear. The present research shows elevated miR-195 but depressed FGF-18 expressed in joint fluid specimens of 20 patients with chronic cartilage lesions and in CH1M and CH3M chondrocytes when compared with that in joint fluid specimens without cartilage lesions and in CH1W and CH2W chondrocytes, respectively. The following loss of function test revealed that downregulation of miR-195 by transfection of miR-195 inhibitors promoted chondrocyte proliferation and expression of a type II collagen α I chain (Col2a1)/aggrecan. Through the online informatics analysis we theoretically predicted that miR-195 could bind to a FGF-18 3' untranslated region (3'UTR), also, we verified that a miR-195 could regulate the FGF-18 and its downstream pathway. The constructed dual luciferase assay further confirmed that FGF-18 was a direct target of miR-195. The executed anti-sense experiment displayed that miR-195 could regulate chondrocyte proliferation and Col2a1/aggrecan expression via the FGF-18 pathway. Finally, through an in vivo anterior cruciate ligament transection (ACLT) model, downregulation of miR-195 presented a significantly protective effect on chronic cartilage lesions. Evaluating all of the outcomes of the current research revealed that a decrease of miR-195 protected chronic cartilage lesions by promoting chondrocyte proliferation and maintenance of chondrogenic phenotypes via the targeting of the FGF-18 pathway and that the miR-195/FGF-18 axis could be a potential target in the treatment of cartilage lesions.

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References

Mithoefer K, Venugopal V, Manaqibwala M . Incidence, Degree, and Clinical Effect of Subchondral Bone Overgrowth After Microfracture in the Knee. Am J Sports Med. 2016; 44(8):2057-63. DOI: 10.1177/0363546516645514. View

Trippel S, Cucchiarini M, Madry H, Shi S, Wang C . Gene therapy for articular cartilage repair. Proc Inst Mech Eng H. 2007; 221(5):451-9. DOI: 10.1243/09544119JEIM237. View

Dasar U, Gursoy S, Akkaya M, Algin O, Isik C, Bozkurt M . Microfracture technique versus carbon fibre rod implantation for treatment of knee articular cartilage lesions. J Orthop Surg (Hong Kong). 2016; 24(2):188-93. DOI: 10.1177/1602400214. View

Almeida M, Silva A, Vasconcelos D, Almeida C, Caires H, Pinto M . miR-195 in human primary mesenchymal stromal/stem cells regulates proliferation, osteogenesis and paracrine effect on angiogenesis. Oncotarget. 2015; 7(1):7-22. PMC: 4807979. DOI: 10.18632/oncotarget.6589. View

Menetrey J, Unno-Veith F, Madry H, Van Breuseghem I . Epidemiology and imaging of the subchondral bone in articular cartilage repair. Knee Surg Sports Traumatol Arthrosc. 2010; 18(4):463-71. DOI: 10.1007/s00167-010-1053-0. View

Liu C, Guan H, Wang Y, Chen M, Xu B, Zhang L . miR-195 Inhibits EMT by Targeting FGF2 in Prostate Cancer Cells. PLoS One. 2015; 10(12):e0144073. PMC: 4674136. DOI: 10.1371/journal.pone.0144073. View

McAlinden A, Varghese N, Wirthlin L, Chang L . Differentially expressed microRNAs in chondrocytes from distinct regions of developing human cartilage. PLoS One. 2013; 8(9):e75012. PMC: 3767648. DOI: 10.1371/journal.pone.0075012. View

Bradley E, Carpio L, Newton A, Westendorf J . Deletion of the PH-domain and Leucine-rich Repeat Protein Phosphatase 1 (Phlpp1) Increases Fibroblast Growth Factor (Fgf) 18 Expression and Promotes Chondrocyte Proliferation. J Biol Chem. 2015; 290(26):16272-80. PMC: 4481226. DOI: 10.1074/jbc.M114.612937. View

Martinez-Sanchez A, Dudek K, Murphy C . Regulation of human chondrocyte function through direct inhibition of cartilage master regulator SOX9 by microRNA-145 (miRNA-145). J Biol Chem. 2011; 287(2):916-24. PMC: 3256897. DOI: 10.1074/jbc.M111.302430. View

10.

Seidl C, Martinez-Sanchez A, Murphy C . Derepression of MicroRNA-138 Contributes to Loss of the Human Articular Chondrocyte Phenotype. Arthritis Rheumatol. 2015; 68(2):398-409. DOI: 10.1002/art.39428. View

11.

Ohbayashi N, Shibayama M, Kurotaki Y, Imanishi M, Fujimori T, Itoh N . FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes Dev. 2002; 16(7):870-9. PMC: 186331. DOI: 10.1101/gad.965702. View

12.

Zhang X, Tao T, Liu C, Guan H, Huang Y, Xu B . Downregulation of miR-195 promotes prostate cancer progression by targeting HMGA1. Oncol Rep. 2016; 36(1):376-82. DOI: 10.3892/or.2016.4797. View

13.

Mori Y, Saito T, Chang S, Kobayashi H, Ladel C, Guehring H . Identification of fibroblast growth factor-18 as a molecule to protect adult articular cartilage by gene expression profiling. J Biol Chem. 2014; 289(14):10192-200. PMC: 3974988. DOI: 10.1074/jbc.M113.524090. View

14.

Cai H, Zhao H, Tang J, Wu H . Serum miR-195 is a diagnostic and prognostic marker for osteosarcoma. J Surg Res. 2014; 194(2):505-510. DOI: 10.1016/j.jss.2014.11.025. View

15.

Hong E, Reddi A . MicroRNAs in chondrogenesis, articular cartilage, and osteoarthritis: implications for tissue engineering. Tissue Eng Part B Rev. 2012; 18(6):445-53. DOI: 10.1089/ten.TEB.2012.0116. View

16.

Hong E, Reddi A . Dedifferentiation and redifferentiation of articular chondrocytes from surface and middle zones: changes in microRNAs-221/-222, -140, and -143/145 expression. Tissue Eng Part A. 2012; 19(7-8):1015-22. DOI: 10.1089/ten.TEA.2012.0055. View

17.

Yasuda H, Oh C, Chen D, de Crombrugghe B, Kim J . A Novel Regulatory Mechanism of Type II Collagen Expression via a SOX9-dependent Enhancer in Intron 6. J Biol Chem. 2016; 292(2):528-538. PMC: 5241729. DOI: 10.1074/jbc.M116.758425. View

18.

Brophy R, Rodeo S, Barnes R, Powell J, Warren R . Knee articular cartilage injuries in the National Football League: epidemiology and treatment approach by team physicians. J Knee Surg. 2009; 22(4):331-8. DOI: 10.1055/s-0030-1247771. View

19.

Gu Y, Rong X, Wen L, Zhu G, Qian M . miR-195 inhibits the proliferation and migration of chondrocytes by targeting GIT1. Mol Med Rep. 2016; 15(1):194-200. DOI: 10.3892/mmr.2016.5982. View

20.

Wang Y, Zhao W, Fu Q . miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma cells. Mol Cell Biochem. 2013; 384(1-2):105-11. DOI: 10.1007/s11010-013-1786-4. View