title: Muscle cell-derived factors inhibit inflammatory stimuli-induced damage in hMSC-derived chondrocytes.
abstract: OBJECTIVE
  Pro-inflammatory cytokines play an important role in inducing cartilage degradation during osteoarthritis pathogenesis. Muscle is a tissue that lies near cartilage in situ. However, muscle's non-loading biochemical effect on cartilage has been largely unexplored. Here, we tested the hypothesis that muscle cells can regulate the response to pro-inflammatory cytokine-mediated damage in chondrocytes derived from human bone marrow-derived mesenchymal stem cells (hMSCs).
  
  
  METHODS
  hMSCs were allowed to undergo chondrogenic differentiation in porous silk scaffolds in the typical chondrogenic medium for 12 days. For the next 9 days, the cells were cultured in chondrogenic medium containing 50% conditioned medium derived from C2C12 muscle cells or fibroblast control cells, and were subject to treatments of pro-inflammatory cytokines IL-1β or TNFα.
  
  
  RESULTS
  Both IL-1β and TNFα-induced strong expression of multiple MMPs and hypertrophic markers Runx2 and type X collagen. Strikingly, culturing hMSC-derived chondrocytes in C2C12 muscle cell-conditioned medium strongly inhibited the expression of all these genes, a result further confirmed by GAG content and histological evaluation of matrix protein. To determine whether these effects were due to altered chondrocyte growth and survival, we assayed the expression of cell proliferation marker Ki67, cell cycle arrest markers p21 and p53, and apoptosis marker caspase 3. Muscle cell-conditioned medium promoted proliferation and inhibited apoptosis, thereby suggesting a possible decrease in the cellular aging and death that typically accompanies cartilage inflammation.
  
  
  CONCLUSIONS
  Our findings suggest the role of muscle in cartilage homeostasis and provide insight into designing strategies for promoting resistance to pro-inflammatory cytokines in hMSC-derived chondrocytes.
authors.affiliation: Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Rainbow
authors.forename: H
authors.initials: H
authors.lastname: Kwon
authors.forename: A T
authors.initials: AT
authors.lastname: Foote
authors.forename: R C
authors.initials: RC
authors.lastname: Preda
authors.forename: D L
authors.initials: DL
authors.lastname: Kaplan
authors.forename: L
authors.initials: L
authors.lastname: Zeng
mesh_terms: D053674:Aggrecans / Q000187:drug effects / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D024043:Collagen Type II / Q000187:drug effects / Q000378:metabolism; D024121:Collagen Type X / Q000187:drug effects / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015683:Gene Products, gag / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D018797:Cell Cycle Proteins; D024043:Collagen Type II; D024121:Collagen Type X; D050659:Core Binding Factor Alpha 1 Subunit; D015683:Gene Products, gag; D053583:Interleukin-1beta; D019394:Ki-67 Antigen; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D020782:Matrix Metalloproteinases