title: Osteoprotegerin inhibits cartilage degradation through an effect on trabecular bone in murine experimental osteoarthritis.
abstract: OBJECTIVE
  To characterize bone microarchitectural changes and to test the hypothesis that disrupting local cytokine equilibrium could modify cartilage degradation in a murine model of experimental osteoarthritis (OA).
  
  
  METHODS
  Ten-week-old male C57BL/6 mice underwent medial meniscectomy of their right knees and a sham operation of their left knees. The mice received intraperitoneal injections of osteoprotegerin (OPG) (10 mg/kg), interleukin-1 receptor antagonist (IL-1Ra) (100 mg/kg), or phosphate buffered saline for 6 weeks. The microarchitecture of the trabecular bone, the OA score, and expression of ADAMTS-4 and ADAMTS-5 were assessed. Proteoglycan release was measured in cartilage explant cultures in the presence of IL-1Ra and OPG.
  
  
  RESULTS
  In the meniscectomized knees, bone volume/tissue volume (BV/TV) was lower, whereas trabecular separation, the OA score, and aggrecanase expression were higher than in the sham-operated knees. After treatment with OPG, BV/TV was significantly increased and trabecular separation was reduced in the knees that underwent meniscectomy. The OA score and the number of ADAMTS-positive cells were significantly decreased by treatment with OPG but were not affected by IL-1Ra. Moreover, OPG did not directly reduce the release of proteoglycans from cartilage explant cultures.
  
  
  CONCLUSIONS
  In an experimental model of OA, meniscectomy induced bone loss and cartilage degradation at 6 weeks. Systemic administration of OPG prevented bone and cartilage degradation in vivo but had no effect on cartilage in vitro. These data collectively indicate that bone could be a contributor in the early stages of OA pathogenesis. They further suggest that disruption of RANKL/OPG balance might result in the degradation of cartilage subjected to mechanical loading. Specific targeting of the bone cytokine network might help to prevent OA.
authors.affiliation: INSERM U606, Université Paris 7, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Kadri
authors.forename: H K
authors.initials: HK
authors.lastname: Ea
authors.forename: C
authors.initials: C
authors.lastname: Bazille
authors.forename: D
authors.initials: D
authors.lastname: Hannouche
authors.forename: F
authors.initials: F
authors.lastname: Lioté
authors.forename: M E
authors.initials: ME
authors.lastname: Cohen-Solal
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002357:Cartilage Diseases / Q000378:metabolism / Q000517:prevention & control*; D002358:Cartilage, Articular / Q000378:metabolism*; D004195:Disease Models, Animal; D053590:Interleukin 1 Receptor Antagonist Protein / Q000502:physiology; D008297:Male; D008592:Menisci, Tibial / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin / Q000502:physiology*; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D053244:Osteoprotegerin; D011509:Proteoglycans; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C498489:Adamts5 protein, mouse; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603919:Adamts4 protein, mouse