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.

Mechanotransduction and the functional response of bone to mechanical strain

Nature has evolved efficient strategies to synthesize complex mineralized structures that exhibit exceptional damage tolerance. One such example is found in the hypermineralized hammer-like dactyl clubs of the stomatopods, a group of highly aggressive marine crustaceans. The dactyl clubs from one species, Odontodactylus scyllarus, exhibit an impressive set of characteristics adapted for surviving high-velocity impacts on the heavily mineralized prey on which they feed. Consisting of a multiphase composite of oriented crystalline hydroxyapatite and amorphous calcium phosphate and carbonate, in conjunction with a highly expanded helicoidal organization of the fibrillar chitinous organic matrix, these structures display several effective lines of defense against catastrophic failure during repetitive high-energy loading events.

https://science.sciencemag.org/content/sci/336/6086/1275.full.pdf

The stomatopod dactyl club : a formidable damage-tolerant biological hammer

When compact bone is subjected to bending loads, interstitial fluid in the bone matrix flows away from regions of high compressive stress. The amount of interstitial fluid flow is strongly influenced by the loading rate in a dose-dependent fashion. We hypothesize that interstitial fluid flow affects bone formation, and we tested this hypothesis indirectly by measuring the effect of different loading frequencies on bone formation rate in vivo. The right tibiae of adult female rats were subjected to applied bending at frequencies of 0.05, 0.1, 0.2, 0.5, 1.0, and 2.0 Hz for a 2-wk period. The rats were then killed and histomorphometric measurements of bone formation were made of the midshaft of the tibia. Bending of the tibia increased bone formation rate in the higher-frequency (0.5 to 2.0 Hz) loading groups as much as fourfold, yet no increase in bone formation rate was observed for loading frequencies below 0.5 Hz. In a separate experiment, we found stress-generated potentials (SGP) in the rat tibia to in...

Mechanotransduction in bone: do bone cells act as sensors of fluid flow?

http://maeresearch.ucsd.edu/mckittrick/pubs/2008_Acta_Biomater_3_587_Crab.pdf

Structure and mechanical properties of crab exoskeletons.

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

Bone tissue engineering: the role of interstitial fluid flow.

The integument of decapod crustaceans consists of an outer epicuticle, an exocuticle, an endocuticle and an inner membranous layer underlain by the hypodermis. The outer three layers of the cuticle are calcified. The mineral is in the form of calcite crystals and amorphous calcium carbonate. In the epicuticle, mineral is in the form of spherulitic calcite islands surrounded by the lipid-protein matrix. In the exo- and endocuticles the calcite crystal aggregates are interspersed with chitin-protein fibers which are organized in lamellae. In some species, the organization of the mineral mirrors that of the organic fibers, but such is not the case in certain cuticular regions in the xanthid crabs. Thus, control of crystal organization is a complex phenomenon unrelated to the gross morphology of the matrix.

Since the cuticle is periodically molted to allow for growth, this necessitates a bidirectional movement of calcium into the cuticle during postmolt and out during premolt resorption of the cuticle. In two species of crabs studied to date, these movements are accomplished by active transport effected by a Ca-ATPase and Na/Ca exchange mechanism.

The epi- and exocuticular layers of the new cuticle are elaborated during premolt but do not calcify until the old cuticle is shed. This phenomenon also occurs in vitro in cuticle devoid of living tissue and implies an alteration of the nucleating sites of the cuticle in the course of the molt.

/pdf/the-structure-and-calcification-of-the-crustacean-cuticle-110ts1pea1.pdf

The Structure and Calcification of the Crustacean Cuticle

Rats, age 28 days, experiencing tail suspension in modified metabolic cages for 1, 2, and 3 wk were compared with littermate controls. Food and water consumption, urinary and fecal Ca excretion, and serum Ca were measured; hearts, fore- and hindlimb bones, skulls, and mandibles were removed for determination of wet, dry, and ash weights and Ca concentration and for histological examination. Weight gain and Ca intake and excretion were the same for both groups; both displayed net Ca gain. Suspended rats had significantly lower wet, dry, and ash weights of femora and tibiae. Dry weights of the humeri and radii/ulnae were moderately higher, and the skull and mandible dry and ash weights were significantly higher in suspended than in control rats. Cortical thickness of the femur, but not humerus, was less in suspended rats. The data are consistent with the hypothesis that bone growth is influenced by the cardiovascular changes associated with tail suspension.

Richard M. Dillaman

Papers

The Structure and Calcification of the Crustacean Cuticle

Bone growth and calcium balance during simulated weightlessness in the rat.