Microgravity-Induced Osteocyte Dysfunction: An Osteocyte Mechanobiology Unit Framework

This review synthesizes evidence from diverse experimental platforms and proposes the Osteocyte Mechanobiology Unit (OMU), a conceptual framework integrating the mechanical and biochemical processes underlying microgravity-induced alterations in osteocytes and their surrounding microenvironment.

Current evidence indicates that microgravity disrupts two interconnected OMU domains: the Mechanical Sensing Domain, through alterations in the local mechanical microenvironment and mechanosensory structures, and the Biochemical Signaling Domain, through dysregulated cellular homeostasis, altered osteocyte functional phenotype, and disrupted intercellular and systemic signaling. This synthesis highlights important knowledge gaps, including the fragmented nature of current evidence, the limited understanding of the relationships among these alterations and their contribution to bone loss, and the need for validation under actual spaceflight conditions. The OMU framework provides a unifying physiological perspective for interpreting fragmented evidence and organizing countermeasures against microgravity-induced bone loss according to the functional domains they target. It also identifies priorities for developing integrated, mechanism-informed strategies to preserve skeletal health during long-duration human spaceflight.