Caveolin‐1 enriched apoptotic bodies derived from oral hard palate orchestrate bone remodeling to treat heterotopic ossification

Heterotopic ossification (HO) is a pathological process characterized by ectopic bone formation in non‐osseous tissues, with an incidence reaching 80% following surgical procedures. Current treatments exhibit limited efficacy, significant rebound effects, and substantial trauma, highlighting the need for safer and more effective therapeutic strategies. This study aimed to explore the therapeutic potential of apoptotic bodies derived from hard palate mesenchymal stromal/stem cells in regulating bone remodeling, and to elucidate the underlying mechanisms, focusing on Caveolin‐1 (CAV1). Transcriptomic analysis of clinical HO samples revealed activation of osteogenesis‐ and calcification‐related pathways. Mechanistically, PMSC‐ABs inhibited osteogenic differentiation while promoting osteoclastogenesis in vitro. Proteomic analysis identified CAV1 as a key functional mediator, which was further validated through functional assays. In a mouse model of HO, systemic administration of PMSC‐ABs reduced ectopic bone formation and suppressed disease progression. These results demonstrate that PMSC‐ABs deliver CAV1 to modulate bone homeostasis, thereby suppressing HO. Our findings suggest that PMSC‐ABs represent a promising, minimally invasive, and effective prophylactic and therapeutic intervention for pathological ossification and related skeletal disorders.