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The Role of the Osteocyte in Mechanotransduction

Current Status

The osteocyte is a mechanosensory, multifunctional cell regulating calcium and phosphate mineral homeostasis and regulating osteoblast and osteoclast function. Whereas mechanosensation and mechanotransduction does not appear to affect the osteocyte’s ability to regulate mineral metabolism, it does play a critical role in the expression of factors that target osteoblasts and osteoclasts.  For example, mechanical loading stimulates the production of factors such as PGE2 and Wnts that have positive effects on osteoblastic bone formation.  Conversely, unloading results in an increase in molecules such as sclerostin which inhibits bone formation and RANKL that promotes osteoclastic bone resorption. Osteocytes form a highly connected intricate network within the bone matrix that can communicate with cells on the bone surface through their dendritic processes, extracellular vesicles and soluble factors. Loading of bone is transmitted though the bone fluid which applies fluid flow shear stress to the cell body and dendrites, but the dendrites have the greatest sensitivity. Osteocytes can live for decades in the bone matrix, however, with age, they osteocyte become susceptible to several states, thought to negatively affect the capacity of the cell to sense mechanical load. Aged cells are exposed to increased reactive oxygen species making the cell more susceptible to apoptosis while at the same time some cells become senescent. A portion of the cells develop a hypermineralized perilacunar matrix, a portion die resulting in empty lacunae that fill in with mineral, called micropetrosis, but the majority develop a senescence-associated secretory phenotype, SASP. This results in a highly compromised osteocyte lacunocanalicular network with fewer cells, fewer dendrites per cell, and less connectivity. This reduced connectivity may be responsible for the loss of bone response to loading. In contrast to the young animal where loading induces new bone formation, in the aged skeleton, there is either little or no response to exercise. Exercise can delay the negative effects of aging and we have found that contracted muscle secreted factors can synergize with suboptimal loading of bone to promote new bone formation. Understanding osteocyte mechanosensation and transduction provides key insights into the beneficial effects of exercise.

Learning Objectives
1). Osteocytes are the key mechanosensory cells in the skeleton.
2).  Mechanically loaded osteocytes produce factors that promote bone formation, whereas unloading induces osteocytes to make factors that promote bone resorption.
3). Aging compromises the osteocyte and its network making the skeleton less responsive to loading.

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