Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone

Abstract

Bone is removed or replaced in defined locations by targeting osteoclasts and osteoblasts in response to its local history of mechanical loading. There is increasing evidence that osteocytes modulate this targeting by their apoptosis, which is associated with locally increased bone resorption. To investigate the role of osteocytes in the control of loading-related modeling or remodeling, we studied the effects on osteocyte viability of short periods of mechanical loading applied to the ulnae of rats. Loading, which produced peak compressive strains of -0.003 or -0.004, was associated with a 78% reduction in the resorption surface at the midshaft. The same loading regimen resulted in a 40% relative reduction in osteocyte apoptosis at the same site 3 days after loading compared with the contralateral side (P = 0.01). The proportion of osteocytes that were apoptotic was inversely related to the estimated local strain (P < 0.02). In contrast, a single short period of loading resulting in strains of -0.008 engendered both tissue microdamage and subsequent bone remodeling and was associated with an eightfold increase in the proportion of apoptotic osteocytes (P = 0.02) at 7 days. This increase in osteocyte apoptosis was transient and preceded both intracortical remodeling and death of half of the osteocytes (P < 0.01). The data suggest that osteocytes might use their U-shaped survival response to strain as a mechanism to influence bone remodeling. We hypothesize that this relationship reflects a causal mechanism by which osteocyte apoptosis regulates bone's structural architecture.

Substrate topography: A valuable in vitro tool, but a clinical red herring for in vivo tenogenesis

“…This observation indicates that although both topography and mechanical stretching can induce similar bidirectional cell elongation, only mechanical loading, in excessive form, can activate apoptotic pathways [61][62][63][64].…”

A theory for bone resorption based on the local rupture of osteocytes cells connections: A finite element study

“…Burr et al [45] showed that within 8 days of the introduction of fatigue microdamage in canine radii by in vivo flexural loading, osteonal Basic Multicellular Unit (BMU) resorption spaces are found in proximity to microcracks about seven times more frequently than would be consistent with random associations. Experiments performed in rats by [37,46] demonstrated that the time dependent migration of osteoclasts into regions of cortical bone containing experimentally induced microdamage have strengthened the argument for the targeting of damage in bone.…”

Is elite sport a driver for medical advance?

“…An elite sport with specificity of microfractures is well established particularly with sports such as running, gymnastics, and rowing (DiFiori et al, 2014). The osteocyte has been shown to undergo apoptotic death at sites of microdamage in bones and to release particular signals for bone destruction at this time (Noble et al, 2003, Kogianni et al, 2008. These signals remain to be identified but are of obvious interest to those in drug discovery for bone health.…”