Apoptotic Bodies Emerge as Key Signaling Units in Bone Homeostasis and Skeletal Disease, Offering Therapeutic Avenues

Bone is one of the most apoptotically active tissues, undergoing continuous remodeling and repair. Historically, apoptotic bodies (ABs) released by dying cells like osteoclasts and osteoblasts were considered mere cellular debris destined for clearance. However, this perspective is evolving. Recent research highlights ABs as sophisticated, source-specific signaling units that carry parent-cell-derived cargo and surface ligands, actively shaping skeletal cell fate, immune responses, and tissue repair. Understanding their precise roles is critical for addressing diseases like osteoporosis and osteoarthritis where bone turnover is dysregulated.

This comprehensive review integrates current evidence on apoptotic bodies (ABs) across skeletal homeostasis and disease. Researchers first defined ABs within the broader extracellular vesicle landscape, addressing heterogeneity, isolation challenges, and terminology. They then systematically examined diverse AB sources and recipient interfaces, including osteoclasts, osteoblast-lineage cells, osteocytes, mesenchymal stem/stromal cells, and immune cells like macrophages. The review further discussed how dysregulated AB signaling contributes to various skeletal pathologies, such as osteoporosis, osteoarthritis, bone metastasis, alveolar bone destruction, and aging-related bone loss, highlighting therapeutic implications.

Apoptotic bodies (ABs) are not inert waste but active signaling units that retain parent-cell cargo and surface ligands, profoundly influencing skeletal cell fate, immune activity, mineralization, and repair. The review detailed how ABs from various sources, including osteoclasts, osteoblasts, and mesenchymal stem/stromal cells, exert distinct effects on recipient cells. Dysregulated AB signaling was identified as a significant contributor to several skeletal diseases, including osteoporosis, osteoarthritis, and bone metastasis. For instance, aberrant AB activity can exacerbate bone loss in aging and contribute to osteochondral mineralization. > The review highlighted therapeutic implications, including AB-based or AB-inspired strategies, such as the cathepsin K (CTSK)-responsive self-assembling peptide nanoparticle OsteoSAVE for in vivo generation of osteoclast-derived ABs (OC-ABs). Furthermore, it hypothesized that existing antiresorptive therapies might reshape OC-AB production, offering a new lens through which to view their mechanisms.