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

• Main Authors: Chubinskaya, S. (Author), Schoeberl, B. (Author), Florine, E. (Author), Kopesky, P. (Author), Li, Yang (Contributor), Grodzinsky, Alan J (Contributor), Wang, Yang (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor)
• Format: Article
• Language: English
• Published: Elsevier, 2017-02-02T18:33:20Z.
• Subjects: Article
• Online Access: Get fulltext

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.
Singapore. Agency for Science, Technology and Research (National Science Scholarship)
Massachusetts Institute of Technology. Office of the Dean for Graduate Education (Chyn Duog Shiah Memorial Graduate Student Fellowship)