Mechanotransduction and the functional response of bone to mechanical strain

Abstract

Mechanotransduction plays a crucial role in the physiology of many tissues including bone. Mechanical loading can inhibit bone resorption and increase bone formation in vivo. In bone, the process of mechanotransduction can be divided into four distinct steps: (1) mechanocoupling, (2) biochemical coupling, (3) transmission of signal, and (4) effector cell response. In mechanocoupling, mechanical loads in vivo cause deformations in bone that stretch bone cells within and lining the bone matrix and create fluid movement within the canaliculae of bone. Dynamic loading, which is associated with extracellular fluid flow and the creation of streaming potentials within bone, is most effective for stimulating new bone formation in vivo. Bone cells in vitro are stimulated to produce second messengers when exposed to fluid flow or mechanical stretch. In biochemical coupling, the possible mechanisms for the coupling of cell-level mechanical signals into intracellular biochemical signals include force transduction through the integrin-cytoskeleton-nuclear matrix structure, stretch-activated cation channels within the 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 entire cell is a mechanosensor and there are many different pathways available for the transduction of a mechanical signal. In the transmission 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 paracrine factors that may signal osteoprogenitors to differentiate into osteoblasts and attach to the bone surface. Insulin-like growth factors and prostaglandins are possible candidates for intermediaries in signal transduction. In the effector cell response, the effects of mechanical loading are dependent upon the magnitude, duration, and rate of the applied load. Longer duration, lower amplitude loading has the same effect on bone formation as loads with short duration and high amplitude. Loading must be cyclic to stimulate new bone formation. Aging greatly reduces the osteogenic effects of mechanical loading in vivo. Also, some hormones may interact with local mechanical signals to change the sensitivity of the sensor or effector cells to mechanical load.

Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading

“…It has been shown that mechanical loading has the ability to suppress bone resorption (3,8,12,26). However, the cellular mechanism that underlies this anti-resorptive effect is not clear.…”

“…Physical loading and routine activities have been shown to inhibit bone resorption that would otherwise occur with disuse (3,8,12,26). However, the cellular mechanism underlying this phenomenon remains largely unknown.…”

Tratamentos não farmacológicos na estimulação da osteogênese

“…23 A deformação mecânica na matriz óssea é transmitida para as células ósseas, o que possibilita alterações na regulação da proliferação celular, diferenciação, morfogênese e expressão genética. 15 A deformação óssea promove diminuição da reabsorção e estimula a formação óssea na região submetida à carga. 22 Pead & Lanyon 44 (1989), ao submeterem o osso à carga externa, observaram número aumentado de osteoblastos na região do periósteo.…”

Mechanical loading of mouse caudal vertebrae increases trabecular and cortical bone mass-dependence on dose and genotype

“…It is well established that insufficient mechanical stimuli, as in the case of prolonged bed rest and hypogravity, lead to massive bone loss. Conversely it has also been demonstrated that mechanical overloading results in enhanced bone formation and a net gain in bone mass (1)(2)(3)(4). These stimuli affect both cortical and trabecular bone in particular trabecular bone which has been shown to have a more enduring sensitivity to mechanical stimulation in human adults (5,6).…”