Next Article in Journal
Recent Advances in Understanding Amino Acid Sensing Mechanisms that Regulate mTORC1
Previous Article in Journal
Diatom Valve Three-Dimensional Representation: A New Imaging Method Based on Combined Microscopies
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(10), 1522; doi:10.3390/ijms17101522

CXCL12/CXCR4 Axis Regulates Aggrecanase Activation and Cartilage Degradation in a Post-Traumatic Osteoarthritis Rat Model

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Cory J. Xian
Received: 30 June 2016 / Revised: 1 September 2016 / Accepted: 5 September 2016 / Published: 29 September 2016
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [4033 KB, uploaded 29 September 2016]   |  

Abstract

We evaluated the role of the CXCL12/CXCR4 (C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4) axis in aggrecanase-mediated cartilage degradation, and explored the underlying mechanism in a post-traumatic osteoarthritis rat model. Expression of CXCL12/CXCR4 and ADAMTS-5 was analyzed in the knees of osteoarthritic and non-arthritic rats using Western blot, ELISA, immunohistochemistry and immunofluorescence. Rodent studies were performed using Sprague-Dawley rats, with animals divided into three groups: Destabilization of the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), DMM/PBS-treated, and sham controls. Rats were sacrificed after eight weeks, and samples were collected for histology and immunohistochemistry analyses. IL-1-pretreated primary chondrocytes were cultured with untreated control, CXCL12a, siNC + CXCL12a, or siRNA CXCR4 + CXCL12a, and analyzed for expression of relevant markers and cellular pathways. Higher levels of CXCL12 were detected in the knee fluid of osteoarthritic subjects, with strong staining for CXCR4 in chondrocytes and CXCL12 in synoviocytes together with enhanced expression of ADAMTS-5. DMM/AMD3100-treated rats showed a significantly reduced immunological response, with minimal evidence of pathology in both histological and immunohistochemical analyses. Treatment with CXCL12a increased the expression of ACAN, RUNX-2, and ADAMTS-4/5 in IL-1-pretreated primary chondrocytes, together with a decrease in the expression of SOX-9. Molecular analyses revealed strong induction of NF-κB activation, along with phosphorylation of MAPKs, and activation of canonical Wnt/β-catenin signaling. In conclusion, inhibition of SDF-1α/CXCR4 signaling axis was able to inhibit aggrecanase expression and lessen cartilage degeneration in post-traumatic osteoarthritis rats. View Full-Text
Keywords: SDF-1α/CXCR4; post-traumatic osteoarthritis (PTOA); ADAMTS-4/5 SDF-1α/CXCR4; post-traumatic osteoarthritis (PTOA); ADAMTS-4/5
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

Lu, W.; Shi, J.; Zhang, J.; Lv, Z.; Guo, F.; Huang, H.; Zhu, W.; Chen, A. CXCL12/CXCR4 Axis Regulates Aggrecanase Activation and Cartilage Degradation in a Post-Traumatic Osteoarthritis Rat Model. Int. J. Mol. Sci. 2016, 17, 1522.

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