32 wk old C3H/HeJ mice actively respond to mechanical loading

Abstract

Numerous studies indicate that C3H/HeJ (C3H) mice are mildly responsive to mechanical loading compared to C57BL/6J (C57) mice. Guided by data indicating high baseline periosteal osteoblast activity in 16 wk C3H mice, we speculated that simply allowing the C3H mice to age until basal periosteal bone formation was equivalent to that of 16 wk C57 mice would restore mechanoresponsiveness in C3H mice. We tested this hypothesis by subjecting the right tibiae of 32 wk old C3H mice and 16 wk old C57 mice to low magnitude rest-inserted loading (peak strain: 1235με) and then exposing the right tibiae of 32 wk C3H mice to low (1085με) or moderate (1875 με) magnitude cyclic loading. The osteoblastic response to loading on the endocortical and periosteal surfaces was evaluated via dynamic histomorphometry. At 32 wk of age, C3H mice responded to low magnitude rest-inserted loading with significantly elevated periosteal mineralizing surface, mineral apposition rate and bone formation compared to unloaded contralateral bones. Surprisingly, the periosteal bone formation induced by low magnitude rest-inserted loading in C3H mice exceeded that induced in 16 wk C57 mice. At 32 wk of age, C3H mice also demonstrated an elevated response to increased magnitudes of cyclic loading. We conclude that a high level of basal osteoblast function in 16 wk C3H mice appears to overwhelm the ability of the tissue to respond to an otherwise anabolic mechanical loading stimulus. However, when basal surface osteoblast activity is equivalent to that of 16 wk C57 mice, C3H mice demonstrate a clear ability to respond to either rest-inserted or cyclic loading.

Separating Fluid Shear Stress from Acceleration during Vibrations In Vitro: Identification of Mechanical Signals Modulating the Cellular Response

“…Previous studies indicated that the cellular responsiveness to mechanical signals can be increased by incorporating rest periods, independent of signal frequency. 39,45 Whether the addition of rest period could normalize the COX-2 response in the 60Hz, 6% dextran group remains to be determined.…”

Bone mechanotransduction may require augmentation in order to strengthen the senescent skeleton

“…Interestingly, Brodt and Silva (Brodt et al 2010) implemented an external loading model to explicitly control for these variables and found that the periosteum of aged and young adult mice equivalently responded to mechanical loading. However, it is clear that the response of the mouse skeleton to mechanical loading is influenced by interactions between age and genotype (Judex et al 2002; Poliachik et al 2008). Thus, it is possible that BALBc mice used in these studies do not suffer age-related suppression of periosteal response to loading as has been observed in other mouse strains and species (Rubin et al 1992; Srinivasan et al 2003; Srinivasan et al 2010; Turner et al 1995).…”

Adaptation of Tibial Structure and Strength to Axial Compression Depends on Loading History in Both C57BL/6 and BALB/c Mice

“…For instance, low-amplitude mechanical stimuli produce greater bone formation rates in C57BL/6 mice than BALB/c [15]. Similarly, C3H/He and C57BL/6 differ in their response to loading [16], but these differences appear to be age-dependent and largely explainable by differences in baseline bone formation between the two strains [17]. The importance of age is further highlighted by the finding that 4 weeks of aging (8 weeks to 12 weeks) in C57BL/6 mice completely alters the trabecular response to tibial loading from gain to loss [2].…”