title: Co-Cr-Mo alloy particles induce tumor necrosis factor alpha production in MLO-Y4 osteocytes: a role for osteocytes in particle-induced inflammation.
abstract: Wear debris-induced osteolysis is purportedly the limiting problem affecting the long term results of joint arthroplasty. Pathogenic effects of wear debris in peri-implant cells such as macrophages, osteoblasts and osteoclasts have been well studied. In contrast, the effects of wear debris on osteocytes, which make up over 90% of all bone cells, remain unknown. We hypothesized that metal implant debris can induce the pro-inflammatory response in osteocytes. This study demonstrated the effects of cobalt-chromium-molybdenum alloy (Co-Cr-Mo) particles on a well-characterized MLO-Y4 osteocyte cell line. Co-Cr-Mo alloy particle treatment significantly (p<0.05) up-regulated tumor necrosis factor alpha (TNFalpha) gene expression after 3 and 6 h and TNFalpha protein production after 24 h, but down-regulated interleukin-6 (IL-6) gene expression after 6 h. Co-Cr-Mo alloy particle treatment also induced osteocyte apoptosis after 24 h. This apoptotic effect was partially (40%) dependent on TNFalpha. Therefore, our results suggest that osteocytes play a role in particle-induced inflammation and bone resorption following total joint arthroplasty by inducing pro-inflammatory cytokines and inducing osteocyte apoptosis.
authors.affiliation: Department of Anatomy and Cell Biology, Rush University Medical Center, 600 South Paulina Street AF507, Chicago, IL 60612, USA.
authors.forename: Arihiko
authors.initials: A
authors.lastname: Kanaji
authors.forename: Marco S
authors.initials: MS
authors.lastname: Caicedo
authors.forename: Amarjit S
authors.initials: AS
authors.lastname: Virdi
authors.forename: D Rick
authors.initials: DR
authors.lastname: Sumner
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Hallab
authors.forename: Kotaro
authors.initials: K
authors.lastname: Sena
mesh_terms: D000818:Animals; D017209:Apoptosis; D001862:Bone Resorption / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D010011:Osteocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014800:Vitallium / Q000009:adverse effects*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014800:Vitallium