title: A potential role of chondroitin sulfate on bone in osteoarthritis: inhibition of prostaglandin E₂ and matrix metalloproteinases synthesis in interleukin-1β-stimulated osteoblasts.
abstract: OBJECTIVE
  To determine the effect of chondroitin sulfate (CS) on inflammatory mediators and proteolytic enzymes induced by interleukin-1β (IL-1β) and related to cartilage catabolism in murine osteoblasts.
  
  
  METHODS
  Osteoblasts were obtained by enzymatic digestion of calvaria from Swiss mice and cultured for 3 weeks as a primary culture. Cells were then stimulated with IL-1β (1 or 10 ng/ml). CS-treated osteoblasts were incubated with 100 μg/ml of CS during the last week of culture w/o IL-1β for the last 24 h. Expressions of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), 15-PG dehydrogenase (15-PGDH), matrix metalloproteinases-3 and -13 (MMP-3 and -13), osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) were determined by real-time polymerase chain reaction (PCR). PGE₂, MMP-3 and MMP-13 release were assessed in the medium by enzyme-linked immunosorbent assay or western-blotting.
  
  
  RESULTS
  IL-1β increased COX-2, mPGES-1, MMP-3, MMP-13, RANKL expressions, decreased 15-PGDH expression, and increased PGE₂, MMP-3 and MMP-13 release. Interestingly, 7 days of CS treatment significantly counteracted IL-1β-induced expression of COX-2 (-62%, P<0.001), mPGES-1 (-63%, P<0.001), MMP-3 (-39%, P=0.08), MMP-13 (-60%, P<0.001) and RANKL (-84%, P<0.001). Accordingly, IL-1β-induced PGE₂, MMP-3 and MMP-13 releases were inhibited by 86% (P<0.001), 58%(P<0.001) and 38% (P<0.01) respectively.
  
  
  CONCLUSIONS
  In conclusion, our data demonstrate that, in an inflammatory context, CS inhibits the production of PGE₂ and MMPs. Since CS has previously been shown to counteract the production of these mediators in chondrocytes, we speculate that the beneficial effect of CS in Osteoarthritis (OA) could not only be due to its action on cartilage but also on subchondral bone.
authors.affiliation: UR 4, University Pierre & Marie Curie Paris VI, Paris Universitas, Aging, Stress and Inflammation Laboratory, 7 quai St-Bernard, 75252 Paris Cedex 5, France.
authors.forename: E
authors.initials: E
authors.lastname: Pecchi
authors.forename: S
authors.initials: S
authors.lastname: Priam
authors.forename: Z
authors.initials: Z
authors.lastname: Mladenovic
authors.forename: M
authors.initials: M
authors.lastname: Gosset
authors.forename: A-S
authors.initials: AS
authors.lastname: Saurel
authors.forename: L
authors.initials: L
authors.lastname: Aguilar
authors.forename: F
authors.initials: F
authors.lastname: Berenbaum
authors.forename: C
authors.initials: C
authors.lastname: Jacques
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006911:Hydroxyprostaglandin Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D053244:Osteoprotegerin / Q000096:biosynthesis; D000071876:Prostaglandin-E Synthases; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D018836:Inflammation Mediators; D053583:Interleukin-1beta; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D002809:Chondroitin Sulfates; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2; D020782:Matrix Metalloproteinases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone