CXCL10 is upregulated in synovium and cartilage following articular fracture

Bridgette D. Furman, Collin L. Kent, Janet L. Huebner, Virginia B. Kraus, Amy L. McNulty, Farshid Guilak, Steven A. Olson

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The objective of this study was to investigate the expression of the chemokine CXCL10 and its role in joint tissues following articular fracture. We hypothesized that CXCL10 is upregulated following articular fracture and contributes to cartilage degradation associated with post-traumatic arthritis (PTA). To evaluate CXCL10 expression following articular fracture, gene expression was quantified in synovial tissue from knee joints of C57BL/6 mice that develop PTA following articular fracture, and MRL/MpJ mice that are protected from PTA. CXCL10 protein expression was assessed in human cartilage in normal, osteoarthritic (OA), and post-traumatic tissue using immunohistochemistry. The effects of exogenous CXCL10, alone and in combination with IL-1, on porcine cartilage explants were assessed by quantifying the release of catabolic mediators. Synovial tissue gene expression of CXCL10 was upregulated by joint trauma, peaking one day in C57BL/6 mice (25-fold) versus 3 days post-fracture in MRL/MpJ mice (15-fold). CXCL10 protein in articular cartilage was most highly expressed following trauma compared with normal and OA tissue. In a dose dependent manner, exogenous CXCL10 significantly reduced total matrix metalloproteinase (MMP) and aggrecanase activity of culture media from cartilage explants. CXCL10 also trended toward a reduction in IL-1α-stimulated total MMP activity (p = 0.09) and S-GAG (p = 0.09), but not NO release. In conclusion, CXCL10 was upregulated in synovium and chondrocytes following trauma. However, exogenous CXCL10 did not induce a catabolic response in cartilage. CXCL10 may play a role in modulating the chondrocyte response to inflammatory stimuli associated with joint injury and the progression of PTA.

Original languageEnglish
Pages (from-to)1220-1227
Number of pages8
JournalJournal of Orthopaedic Research
Volume36
Issue number4
DOIs
StatePublished - Apr 2018

Keywords

  • arthritis
  • chemokine
  • inflammation
  • injury
  • intra-articular fracture

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