WNT5A-Associated Osteogenic Enhancement Contributes to the Protective Effects of OPG-Fc in Glucocorticoid-Associated Femoral Head Osteonecrosis

, OPG-Fc promoted osteogenic differentiation while inhibiting adipogenic differentiation of BMSCs. Transcriptome and protein analyses revealed significantly higher WNT5A expression following OPG-Fc treatment. Importantly, pharmacological blockade of WNT5A with box5 and Wnt5a knockdown partially attenuated OPG-Fc-associated pro-osteogenic effects, whereas box5 had limited effects on anti-resorptive marker changes. These findings suggest that OPG-Fc exerts dual protective actions in SONFH by suppressing bone resorption and enhancing osteogenic differentiation in association with WNT5A-related signaling. This study provides new mechanistic insights into RANKL blockade therapy and offers a potential molecular target for early intervention in SONFH.