Combining <i>TNF-α</i> silencing with <i>Wnt3a</i> overexpression: a promising gene therapy for particle-induced periprosthetic osteolysis.

ABSTRACT: Wear particle-induced periprosthetic osteolysis is a prevalent issue that frequently leads to the failure of joint replacements, necessitating the development of effective therapeutic strategies. In this study, we established a mouse model of prosthetic loosening and evaluated the therapeutic effects of targeting tumor necrosis factor-alpha (TNF-α) and wingless-type MMTV integration site family, member 3A (Wnt3a) on osteolysis. TNF-α knockdown reduced inflammation and osteoclast-related gene expression, while Wnt3a overexpression increased osteoblast-related gene expression. Notably, the combination of these interventions showed superior efficacy in inhibiting osteolysis compared to monotherapy. Biomechanical imaging and histological staining revealed that combi

SUBMITTER: Chen P 

PROVIDER: S-EPMC11922860 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature