MECHANOTRANSDUCTION AND THE FUNCTIONAL-RESPONSE OF BONE TO MECHANICALSTRAIN

Mechanotransduction plays a crucial role in the physiology of many tis sues including bone. Mechanical loading can inhibit bone resorption an d increase bone formation in vivo. In bone, the process of mechanotran sduction can be divided into four distinct steps: (1) mechanocoupling, (2) biochemical coupling, (3) transmission of signal, and (4) effecto r cell response. In mechanocoupling, mechanical loads in vivo cause de formations in bone that stretch bone cells within and lining the bone matrix and create fluid movement within the canaliculae of bone. Dynam ic loading, which is associated with extracellular fluid flow and the creation of streaming potentials within bone, is most effective for st imulating new bone formation in vivo. Bone cells in vitro are stimulat ed to produce second messengers when exposed to fluid flow or mechanic al stretch. In biochemical coupling, the possible mechanisms for the c oupling of cell-level mechanical signals into intracellular biochemica l signals include force transduction through the integrin-cytoskeleton -nuclear matrix structure, stretch-activated cation channels within th e cell membrane, G protein-dependent pathways, and linkage between the cytoskeleton and the phospholipase C or phospholipase A pathways. The tight interaction of each of these pathways would suggest that the en tire cell is a mechanosensor and there are many different pathways ava ilable for the transduction of a mechanical signal. In the transmissio n of signal, osteoblasts, osteocytes, and bone lining cells may act as sensors of mechanical signals and may communicate the signal through cell processes connected by gap junctions. These cells also produce pa racrine factors that may signal osteoprogenitors to differentiate into osteoblasts and attach to the bone surface. Insulin-like growth facto rs and prostaglandins are possible candidates for intermediaries in si gnal transduction. In the effector cell response, the effects of mecha nical loading are dependent upon the magnitude, duration, and rate of the applied load. Longer duration, lower amplitude loading has the sam e effect on bone formation as loads with short duration and high ampli tude. Loading must be cyclic to stimulate new bone formation. Aging gr eatly reduces the osteogenic effects of mechanical loading in vivo. Al so, some hormones may interact with local mechanical signals to change the sensitivity of the sensor or effector cells to mechanical load.