Tnf-alpha and Rankl Cooperatively Mediate Implant Particle-induced Osteoclastogenesis via Distinct Actions

Introduction: Periprosthetic osteolysis stimulated by implant particulate debris is mediated by various pro-inflammatory cytokines (TNF-alpha, IL-1, and IL-6) that enhance osteoclast differentiation and activity, yet TNF-alpha (TNF) has recently been identified as playing a critical role in this process (1,2). Specifically, in osteoclast precursor cells implant particles activate the nuclear transcription factor NF-kB via a TNF-dependent pathway (3). This is a fundamental signalling mechanism since NF-kB is mandatory for normal osteoclast development and function. RANKL (receptor activator of NF-kB ligand, also known as ODF, OPGL) is a member of the TNF superfamily that also stimulates osteoclastogenesis and has recently been implicated in having a role in particle-induced bone resorption. The activity of RANKL is inhibited by a soluble decoy receptor called osteoprotegrin (OPG). Presently, the specific roles and interaction of TNF and RANKL in particle-induced osteoclastogenesis are not understood. Thus, we have investigated the distinct actions of these potent osteoclastogenic factors in polymethylmethacrylate (PMMA) particle-induced osteoclastogenesis in vitro.