Table 1 Role of essential cells implicated in osteolysis pathogenesis

Monocyte/macrophage

Dominant cell type implicated in osteolysis: vastly present in periprosthetic tissue and pseudosynovial membrane, and correlated with bone resorption^{5–8,22,28–31}

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 formation^7,42,44

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 signaling^6,102

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 membrane^9,40

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