Next Article in Journal
Transposable Elements in Human Cancer: Causes and Consequences of Deregulation
Next Article in Special Issue
A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration
Previous Article in Journal
Galectin-3 in Peripheral Artery Disease. Relationships with Markers of Oxidative Stress and Inflammation
Previous Article in Special Issue
Role of RHEB in Regulating Differentiation Fate of Mesenchymal Stem Cells for Cartilage and Bone Regeneration
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(5), 975; doi:10.3390/ijms18050975

Decrease of miR-195 Promotes Chondrocytes Proliferation and Maintenance of Chondrogenic Phenotype via Targeting FGF-18 Pathway

1
Department of Joint Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
2
The 4th Department of Orthopedic Surgery, The Central Hospital Affiliated to Shenyang Medical College, Shenyang 110024, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Cory J. Xian
Received: 21 March 2017 / Revised: 21 April 2017 / Accepted: 24 April 2017 / Published: 4 May 2017
(This article belongs to the Special Issue Advances in Bone and Cartilage Research)
View Full-Text   |   Download PDF [13564 KB, uploaded 4 May 2017]   |  

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. View Full-Text
Keywords: miR-195; FGF18; cartilage lesion; chondrocyte proliferation; Col2a1/aggrecan; signal pathway miR-195; FGF18; cartilage lesion; chondrocyte proliferation; Col2a1/aggrecan; signal pathway
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Wang, Y.; Yang, T.; Liu, Y.; Zhao, W.; Zhang, Z.; Lu, M.; Zhang, W. Decrease of miR-195 Promotes Chondrocytes Proliferation and Maintenance of Chondrogenic Phenotype via Targeting FGF-18 Pathway. Int. J. Mol. Sci. 2017, 18, 975.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top