title: Effects of insulin-like growth factor-1 and dexamethasone on cytokine-challenged cartilage: relevance to post-traumatic osteoarthritis.
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.
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Rush University Medical Center, Chicago, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chubinskaya
authors.affiliation: Merrimack Pharmaceuticals, USA.
authors.forename: B
authors.initials: B
authors.lastname: Schoeberl
authors.affiliation: Merrimack Pharmaceuticals, USA.
authors.forename: E
authors.initials: E
authors.lastname: Florine
authors.affiliation: Merrimack Pharmaceuticals, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kopesky
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: alg@mit.edu.
authors.forename: A J
authors.initials: AJ
authors.lastname: Grodzinsky
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000293:injuries*; D002417:Cattle; D016207:Cytokines / Q000008:administration & dosage; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000627:therapeutic use; D053582:Interleukin-1alpha / Q000008:administration & dosage; D010003:Osteoarthritis / Q000209:etiology* / Q000517:prevention & control
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D053582:Interleukin-1alpha; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone
keywords: Cartilage; Cytokine; Glucocorticoid; Growth factor; Post-traumatic osteoarthritis