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Two distinct cellular mechanisms of osteoclast formation and bone resorption in periprosthetic osteolysis
Author(s) -
Sabokbar A.,
Kudo O.,
Athanasou N. A.
Publication year - 2003
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1016/s0736-0266(02)00106-7
Subject(s) - rankl , osteoclast , bone resorption , cd14 , osteoprotegerin , resorption , microbiology and biotechnology , chemistry , rank ligand , tumor necrosis factor alpha , proinflammatory cytokine , cytokine , tartrate resistant acid phosphatase , medicine , endocrinology , immunology , receptor , cancer research , biology , inflammation , activator (genetics)
Purpose : TNFα and IL‐1α are proinflammatory cytokines that are abundant in periprosthetic tissues. These cytokines stimulate bone resorption and have recently been shown to directly induce osteoclast formation in mouse marrow cultures. We examined whether TNFα and IL‐1α can directly induce osteoclast formation from human arthroplasty‐derived (CD14 + ) macrophages by a mechanism independent of RANKL‐induced osteoclastogenesis. Methods : TNFα and M‐CSF (±IL‐1α) were added to cultures of magnetically sorted (CD14 + ) and unsorted (CD14 + /CD14 −14 ) cells isolated from the pseudomembrane of loosened hip arthroplasties. Osteoprotegerin (OPG), RANK:Fc and antibodies to TNF receptors (p55 and p75) were added to these cultures to distinguish the pathway of osteoclastogenesis. Osteoclast differentiation was assessed by expression of tartrate‐resistant acid phosphatase (TRAP), vitronectin receptor (VNR) and lacunar resorption. Results : The addition of TNFα (±IL‐1α) resulted in differentiation of CD14 + macrophages into TRAP + and VNR + multinucleated cells capable of extensive lacunar resorption. Both OPG and RANK:Fc (which inhibit RANKL‐induced osteoclastogenesis) did not block osteoclastogenesis. The addition of antibodies directed against the p55 receptor subunit of TNF resulted in significant inhibition of osteoclast formation and lacunar resorption. Conclusions : Our results indicate that, in the presence of M‐CSF, TNFα is sufficient for inducing human osteoclast differentiation from arthroplasty macrophages and that TNFα acts synergistically with IL‐1α to stimulate lacunar resorption. This process is distinct from the RANK/RANKL signalling pathway and is likely to operate in periprosthetic tissues when there is heavy wear particle deposition and cytokine production. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.