title: Oestrogen deficiency modulates particle-induced osteolysis.
abstract: BACKGROUND
  Postmenopausal osteoporosis may modulate bone response to wear debris. In this article, we evaluate the influence of oestrogen deficiency on experimental particle-induced osteolysis.
  
  
  METHODS
  Polyethylene (PE) particles were implanted onto the calvaria of normal controls, sham-ovariectomized (OVX), OVX mice and OVX mice supplemented with oestrogen (OVX+E). After 14 days, seven skulls per group were analyzed using a high-resolution micro-computed tomography (micro-CT) and histomorphometry, and for tartrate-specific alkaline phosphatase. Five calvariae per group were cultured for the assay of IL-1β, IL-6, TNF-α and receptor activator of the nuclear factor κB (RANKL) secretion using quantitative ELISA. Serum IL-6 concentrations were obtained. The expression of RANKL and osteoprotegerin (OPG) mRNA were evaluated using real-time PCR.
  
  
  RESULTS
  As assessed by μCT and by histomorphometry, PE particles induced extensive bone resorption and an intense inflammatory reaction in normal controls, sham-OVX and OVX+E mice, but not in the OVX mice group. In normal controls, sham-OVX and OVX+E mice, PE particles induced an increase in serum IL-6, in TNF-α and RANKL local concentrations, and resulted in a significant increase in RANKL/OPG messenger RNA (mRNA) ratio. Conversely, these parameters remained unchanged in OVX mice after PE implantation.
  
  
  CONCLUSIONS
  Oestrogen privation in the osteolysis murine model ultimately attenuated osteolytic response to PE particles, suggesting a protective effect. This paradoxical phenomenon was associated with a down-regulation of pro-resorptive cytokines. It is hypothesized that excessive inflammatory response was controlled, illustrated by the absence of increase of serum IL-6 in OVX mice after PE implantation.
authors.affiliation: Laboratoire de Bioingénierie et Biomécanique Ostéo-articulaires, Faculté de Médecine Paris 7-Denis Diderot, 10, avenue de Verdun, 75010 Paris, France. chrnich@gmail.com
authors.forename: Christophe
authors.initials: C
authors.lastname: Nich
authors.forename: Jean
authors.initials: J
authors.lastname: Langlois
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchadier
authors.forename: Catherine
authors.initials: C
authors.lastname: Vidal
authors.forename: Martine
authors.initials: M
authors.lastname: Cohen-Solal
authors.forename: Hervé
authors.initials: H
authors.lastname: Petite
authors.forename: Moussa
authors.initials: M
authors.lastname: Hamadouche
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D010014:Osteolysis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D010024:Osteoporosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D010052:Ovariectomy; D020959:Polyethylene / Q000633:toxicity*; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics / Q000378:metabolism; D012886:Skull / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D004967:Estrogens; D053583:Interleukin-1beta; D015850:Interleukin-6; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D020959:Polyethylene