Table 1. Role of essential cells implicated in osteolysis pathogenesis.

Cell type	Role	Comments
Monocyte/macrophage	Dominant cell type implicated in osteolysis: vastly present in periprosthetic tissue and pseudosynovial membrane, and correlated with bone resorption5–8,22,28–31 Secrete MMPs, TNF-α, IL-1β, IL-6, and eicosanoids after phagocytosis of wear debris101 Systemic migration contributes to local infiltration, osteoclast differentiation, and bone destruction28 Increased peripheral CD14+CD16+ phenotype frequency; correlated with increased baseline level and production of TNF-α and IL-1β52	Potent, proinflammatory phenotype
Dendritic cell	Infiltrate and surround UHMWPE particles, participating in phagocytosis and MGC formation7,42,44 Produce proinflammatory cytokines IL-1, IL-6, IL-12, TNF-α, and IFN-γ 7,42,44,46 Compose prosthetic synovial pseudomembrane7	Ultimately results in NALP3 inflammasome activation and enzymatic bone resorption; likely paralleling macrophage function Contributes to osteoclastogenesis and activation
Osteoblast	Able to phagocytose wear particles and alter cellular signaling6,102 Decrease OPG secretion when challenged with PE in vitro103 Express RANKL104 and M-CSF105 upon TNF-α and IL-1β stimulation in vitro Dose-dependent decrease in proliferation, differentiation, and mineralization when challenged with UHMWPE particles in vitro102 Decreased expression of procollagen α1 mRNA and synthesis of collagen I in vitro by phagocytic- dependent and -independent mechanisms when challenged with PE particles101 Increased expression of IL-6101 and IL-8103 when challenged with PE in vitro
Fibroblast	Present in pseudosynovial periprosthetic membrane9,40 Expresses RANKL and can induce osteoclast differentiation in pseudosynovial membrane106 Activated by TNF-α and IL-1β and produce MMPs and cytokines in titanium wear107 and osteoarthritis108 models In tissues exposed to PE, possess MMP2 mRNA alongside macrophages and MGCs expressing MMPs 2 and 14 protein but only MMP14 mRNA109	Likely activated by TNF-α and IL-1β in presence of PE as well, contributing to inflammation Suggests cooperation with macrophages in local tissue destruction

IL-1, interleukin-1; IFN-γ, interferon-γ; M-CSF, macrophage colony-stimulating factor; MGC, multinucleated giant cell; MMP, matrix metalloproteinase; OPG, osteoprotegerin; PE, polyethylene; RANKL, receptor activator of nuclear factor-κB ligand; TNF-α, tumor necrosis factor-α; UHMWPE, ultra-high molecular weight polyethylene.