TABLE 1.

Key cytokines involved in periprosthetic osteolysis and their pathogenic roles.

Cytokine	Primary cellular source	Signaling target/Pathway	Pathological role in PPO	Key references
TNF-α	M1 macrophages, T cells, fibroblasts	TNFR1 → NF-κB, MAPK	Induces RANKL expression, directly promotes osteoclastogenesis, and stimulates IL-6/PGE2	Ge et al. (2018), Schwarz et al. (2000)
IL-1β	Macrophages, synovial cells	IL-1R → NF-κB, Wnt/β-catenin	Activates MMPs and PGE2, enhances TNF-α signaling, facilitates matrix degradation	Kusano et al. (1998), Yu and Canalis (2020)
IL-6	Osteoblasts, macrophages	IL-6R/gp130 → JAK/STAT3	Increases RANKL/OPG imbalance, sensitizes osteoclast precursors to RANKL	Feng et al. (2017), McGregor et al. (2019)
IL-10	M2 macrophages, Treg cells	IL-10R → STAT3	Suppresses MMPs, stimulates OPG production, promotes resolution of inflammation	Souza and Lerner (2013), Ye et al. (2011)
IL-17	Th17 cells	IL-17R → NF-κB, MAPK	Promotes sclerostin expression, enhances RANKL and Cathepsin K activity	Jiao et al. (2023), Zhang et al. (2020b)
MCP-1	Macrophages, fibroblasts	CCR2-mediated chemotaxis	Recruits inflammatory cells (monocytes/macrophages) and maintains inflammatory microenvironment	Deshmane et al. (2009), Gschwandtner et al. (2019)
MIP-1α	M1 macrophages, osteoblasts	CCR1/CCR5 pathway	Promotes osteoclast precursor recruitment and enhances resorptive activity	Gao et al. (2018a), Jämsen et al. (2017), Wang et al. (2022c)
IFN-γ	NK cells, Th1 cells	TRAF6-dependent, MHC pathways	Inhibits osteoclastogenesis via TRAF6 degradation but promotes antigen presentation	Niu et al. (2022), Takayanagi et al. (2000)
PGE2	Fibroblasts, macrophages	EP receptors → cAMP/PKA	Enhances osteoclastogenesis in synergy with TNF-α and IL-1β	Lader and Flanagan (1998), Sheibanie et al. (2007)