Journal
OSTEOARTHRITIS AND CARTILAGE
Volume 23, Issue 11, Pages 1879-1889Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2015.06.021
Keywords
Cartilage; Injury; Synovium; Inflammation; Fibrotic scar; Hyaluronan synthases
Categories
Funding
- NIH [R01-AR057066]
- Arthritis Foundation
- Seikagaku Corporation (DCC)
- Katz-Rubschlager Endowment for OA Research
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Objective: Articular cartilage defects commonly result from traumatic injury and predispose to degenerative joint diseases. To test the hypothesis that aberrant healing responses and chronic inflammation lead to osteoarthritis (OA), we examined spatiotemporal changes in joint tissues after cartilage injury in murine knees. Since intra-articular injection of hyaluronan (HA) can attenuate injury-induced osteoarthritis in wild-type (WT) mice, we investigated a role for HA in the response to cartilage injury in mice lacking HA synthase 1 (Has1(-/-)). Design: Femoral groove cartilage of WT and Has1(-/-) mice was debrided to generate a non-bleeding wound. Macroscopic imaging, histology, and gene expression were used to evaluate naive, sham-operated, and injured joints. Results: Acute responses (1-2 weeks) in injured joints from WT mice included synovial hyperplasia with HA deposition and joint-wide increases in expression of genes associated with inflammation, fibrosis, and extracellular matrix (ECM) production. By 4 weeks, some resurfacing of damaged cartilage occurred, and early cell responses were normalized. Cartilage damage in Has1(-/-) mice also induced early responses; however, at 4 weeks, inflammation and fibrosis genes remained elevated with widespread cartilage degeneration and fibrotic scarring in the synovium and joint capsule. Conclusions: We conclude that the ineffective repair of injured cartilage in Has1(-/-) joints can be at least partly explained by the markedly enhanced expression of particular genes in pathways linked to ECM turnover, IL-17/IL-6 cytokine signaling, and apoptosis. Notably, Has1 ablation does not alter gross HA content in the ECM, suggesting that HAS1 has a unique function in the metabolism of inflammatory HA matrices. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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