Conditional deletion of Wnt5a in myeloid osteoclast precursors results in low bone mass via disruption of osteoblast migration and focal adhesion dynamics

Transcriptomic profiling of osteoblast-enriched cells revealed dysregulation of genes involved in cell adhesion, integrin binding, and cell communication, alongside upregulation of stress-related genes. Histological analyses and functional assays showed that loss of osteoclast-derived Wnt5a led to impaired extracellular matrix maturation together with defective osteoblast focal adhesion assembly and migration, respectively.

Collectively, these data provide a mechanistic link between Wnt5a and osteoblast function. In summary, our study establishes osteoclast-derived Wnt5a as a clastokine supporting bone formation through regulation of osteoblast migration and adhesion dynamics, highlighting the context-dependent and cell-specific roles of WNT5A in skeletal homeostasis.