Effects of insulin-like growth factor-1 and dexamethasone on cytokine-challenged cartilage: Relevance to post-traumatic osteoarthritis

Y. Li, Y. Wang, S. Chubinskaya, B. Schoeberl, E. Florine, P. Kopesky, A. J. Grodzinsky

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

Objective: Interleukin-1 is one of the inflammatory cytokines elevated after traumatic joint injury that plays a critical role in mediating cartilage tissue degradation, suppressing matrix biosynthesis, and inducing chondrocyte apoptosis, events associated with progression to post-traumatic osteoarthritis (PTOA). We studied the combined use of insulin-like growth factor-1 (IGF-1) and dexamethasone (Dex) to block these multiple degradative effects of cytokine challenge to articular cartilage. Methods: Young bovine and adult human articular cartilage explants were treated with IL-1α in the presence or absence of IGF-1, Dex, or their combination. Loss of sulfated glycosaminoglycans (sGAG) and collagen were evaluated by the DMMB and hydroxyproline assays, respectively. Matrix biosynthesis was measured via radiolabel incorporation, chondrocyte gene expression by qRT-PCR, and cell viability by fluorescence staining. Results: In young bovine cartilage, the combination of IGF-1 and Dex significantly inhibited the loss of sGAG and collagen, rescued the suppression of matrix biosynthesis, and inhibited the loss of chondrocyte viability caused by IL-1α treatment. In adult human cartilage, only IGF-1 rescued matrix biosynthesis and only Dex inhibited sGAG loss and improved cell viability. Thus, the combination of IGF-1+Dex together showed combined beneficial effects in human cartilage. Conclusions: Our findings suggest that the combination of IGF-1 and Dex has greater beneficial effects than either molecule alone in preventing cytokine-mediated cartilage degradation in adult human and young bovine cartilage. Our results support the use of such a combined approach as a potential treatment relevant to early cartilage degradative changes associated with joint injury.

Original languageEnglish (US)
Pages (from-to)266-274
Number of pages9
JournalOsteoarthritis and Cartilage
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2015
Externally publishedYes

Keywords

  • Cartilage
  • Cytokine
  • Glucocorticoid
  • Growth factor
  • Post-traumatic osteoarthritis

ASJC Scopus subject areas

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine

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