Function of Osteocytes in Bone—Their Role in Mechanotransduction

Abstract

Although osteocytes are by far the most abundant cell type of bone, they are least understood in terms of function and regulation. Previous studies have concentrated on their possible role as mobilizers of bone calcium, via the process of osteocytic osteolysis. Currently, however, their possible involvement in mechanical adaptation, the process whereby bone tissue maintains maximal functional strength with minimal bone mass, is discussed. We have recently obtained experimental evidence that osteocytes are the mechanosensory cells of bone, involved in the transduction of mechanical loads into biochemical signals. Our results support the hypothesis that flow of fluid through the lacunar-canalicular system as a result of loading provides the physical signal that activates the cells.

The effect of mechanical strain on soft (cardiovascular) and hard (bone) tissues

“…[3][4][5] Many experimental data in vitro and in vivo indicate the osteocytes as the main sensor detecting mechanical forces in the bone tissue. [6][7][8][9] Osteocytes comprise 90-95% of all bone cells in the adult skeleton, and they are located in the mineralized bone matrix within lacunae. Indeed, they have many cytoplasmic processes that stretch out within bone matrix channels called canaliculi.…”

Roles of gap junctions and hemichannels in bone cell functions and in signal transmission of mechanical stress

“…Furthermore, bone cells including osteoblasts and osteocytes are more sensitive to fluid flow shear stress than mechanical strain, stretching and compression (136)(137)(138)(139)(140). Theoretical models and other experimental evidence also suggest that osteocytes are the most likely mechosensor cells in the bone and shear stress induced by fluid flow shear stress is the major mechanism of mechanical loading (130)(131)(132)(141)(142)(143)(144)(145)(146). A cable model predicts that the diffusion time for the spread of current along the membrane of the osteocytic processes is about 0.03 seconds, close to the same predicted pore pressure relaxation time for the draining of the bone fluid into the osteonal canal (147).…”

Fluid Flow Sensitivity of Bone Cells as a Function of Age

“…However, the bones of mature rats adapt better to unaccustomed mechanical loading than do the bones of old rats (46). It is widely believed that bone cells mediate bone adaptations to mechanical loading by activating signaling pathways that regulate bone modeling and remodeling (7,8,11,15). We found that Caf + signaling in ensembles of osteoblastic cells was dependent on the frequency and magnitude of a mechanical stimulus.…”

“…To this end, researchers have recently begun to investigate mechanotransduction mechanisms (15,17,32) in an attempt to better uncover the elusive signal transduction pathways by which physical stimuli can affect cellular responses in bone. These studies have found that bone cells can respond to a wide variety of endogenously occurring signals including mechanical stretch (41), streaming potentials, chemotransport, electrical effects (2,6,26,33), and fluid flow (8,17,28,41). In the latter area of research, it has been hypothesized that the fluid flow through the lacunar-canalicular network is pivotal to bone cell responsiveness.…”

“…For PGE 2 and Ca 2+ experiments, bone cells were placed in a parallel plate flow chamber and subjected to oscillatory fluid flow. This system has been previously characterized, and we and others have employed it to expose endothelial cells (8), chondrocytes (37,38), and bone cells (14,15,17,41) to physiological levels of fluid flow. Briefly, the system imparts a laminar flow to the cells in a monolayer, exposing them to a shear stress governed by the equation (9) T = ß^Q/bh 2 where T is the shear stress, |x is the viscosity of the flow medium, Q is the flow rate, and b and h are the width and height of the chamber, respectively.…”