Deletion of ATAD3A inhibits osteogenesis by impairing mitochondria structure and function in pre-osteoblast

ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear encoded mitochondrial membrane protein that spans inner and outer membrane, and it has been shown to regulate mitochondrial dynamics and cholesterol metabolism. Since the mitochondrial functions have been implicated for osteogenic differentiation, a role of ATAD3A in skeletal development has been investigated.

Mesenchyme-specific ATAD3 knockout mice displayed severe defects in skeletal development. Additionally, osteoblast-specific deletion of ATAD3 in mice caused significant reduction in bone mass, while cartilage-specific ATAD3 knockout mice did not show any significant phenotypes. Consistent with these in vivo findings, ATAD3A knockdown impaired mitochondrial morphology and function in calvarial pre-osteoblast cultures, which, in turn, suppressed osteogenic differentiation in vitro.

The current findings suggest that ATAD3A plays a crucial role in mitochondria homeostasis, which is required for osteogenic differentiation during skeletal development.