Mechanical forces, osteocyte viability and bone strength

Mechanical loading is critical for the maintenance of bone mass; and reduced physical activity as in old age, bed rest or space flight, invariably leads to bone loss. However, the cellular and molecular mechanisms responsible for these phenomena are poorly understood. Osteocytes, former osteoblasts entombed in the bone matrix, form an extensive cell communication network that is thought to detect mechanical strains and to transmit signals leading to compensatory bone loss or gain. Bone active hormones and drugs control the integrity of this network by regulating osteocyte apoptosis, which might be a determinant of bone strength. Recent findings show that mechanical forces are transmitted into intracellular signaling by integrins and cytoskeletal and catalytic molecules assembled in caveolae, and culminate in activation of ERKs and attenuation of osteocyte apoptosis. Conversely, reduction of mechanical forces in the murine model of unloading by tail suspension increases osteocyte apoptosis; and this event precedes temporally, and is spatially associated with, osteoclast‐mediated resorption and loss of mineral and strength. The evidence linking mechanical stimulation, activation of an integrin/cytoskeleton/Src/ERK signaling pathway, and osteocyte survival provides a mechanistic basis for the profound role of mechanical forces, or lack thereof, on skeletal health and disease.