title: Potential role of hyaluronic acid on bone in osteoarthritis: matrix metalloproteinases, aggrecanases, and RANKL expression are partially prevented by hyaluronic acid in interleukin 1-stimulated osteoblasts.
abstract: OBJECTIVE
  To determine the effect of hyaluronic acid (HA) on proteolytic enzymes and bone remodeling mediators induced by interleukin 1β (IL-1β) and related to cartilage catabolism in murine osteoblasts.
  
  
  METHODS
  Osteoblasts were obtained from Swiss mice and cultured for 3 weeks. HA-treated osteoblasts were incubated with 100 μg/ml HA during the last week of culture, then stimulated with IL-1β (10 ng/ml) for 24 h. The expression of matrix metalloproteinases 3 and 13 (MMP-3 and MMP-13), ADAMTS-4 and ADAMTS-5, tissue inhibitor of metalloproteinases (TIMP), osteoprotegerin, and receptor activator of nuclear factor-κB ligand (RANKL) was determined by real-time polymerase chain reaction. MMP-3 and MMP-13 release was assessed by Western blot analysis.
  
  
  RESULTS
  IL-1β increased the mRNA levels of MMP-3 and MMP-13 and ADAMTS-4 and ADAMTS-5 and release of MMP-3 and MMP-13. Seven days of HA treatment significantly prevented the IL-1β-increased mRNA levels of MMP-3 (-61%, p < 0.01), MMP-13 (-56%, p < 0.01), ADAMTS-4 (-58%, p < 0.05), ADAMTS-5 (-52%, p < 0.01), and RANKL (-49%, p < 0.05), but not TIMP. As well, IL-1β-induced production of MMP-3 and MMP-13 was inhibited, by 27% (p < 0.01) and 40% (p < 0.01), respectively.
  
  
  CONCLUSIONS
  In an inflammatory context in murine osteoblasts, HA can inhibit the expression of MMP and ADAMTS. Because HA can counteract the production of these mediators in chondrocytes, its beneficial effect in osteoarthritis may be due to its action on cartilage and subchondral bone.
authors.affiliation: From the University Pierre and Marie Curie, Paris; Pierre Fabre Laboratories, Castres; Labex Transimmunomics, DHU i2B, Paris; Department of Rheumatology, AP-HP Saint-Antoine Hospital, Paris, France.
authors.forename: Zvezdana
authors.initials: Z
authors.lastname: Mladenovic
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Saurel
authors.forename: Francis
authors.initials: F
authors.lastname: Berenbaum
authors.forename: Claire
authors.initials: C
authors.lastname: Jacques
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006820:Hyaluronic Acid / Q000378:metabolism* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010003:Osteoarthritis / Q000188:drug therapy* / Q000201:enzymology; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology; D061251:Primary Cell Culture; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012886:Skull / Q000166:cytology / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D055675:Viscosupplements / Q000378:metabolism / Q000494:pharmacology
chemical_list: D053583:Interleukin-1beta; D053245:RANK Ligand; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; C505689:Tnfsf11 protein, mouse; D055675:Viscosupplements; D006820:Hyaluronic Acid; D010450:Endopeptidases; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C498489:Adamts5 protein, mouse; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C507081:Mmp13 protein, mouse; D011348:Procollagen N-Endopeptidase; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse; D000071121:ADAMTS4 Protein; C000603919:Adamts4 protein, mouse; C083641:aggrecanase
keywords: ADAMTS; HYALURONIC ACID; METALLOPROTEINASES; OSTEOBLASTS; RANK LIGAND; TISSUE INHIBITOR OF METALLOPROTEINASES