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: 1235 mu epsilon) and then exposing the right tibiae of 32 wk C3H mice to low (1085 mu epsilon) or moderate (1875 mu epsilon) 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.

Figure 1

Endocortical and periosteal (mean + SE) MS/BS (A), MAR (B) and BFR/BS (C) induced by rest-inserted mechanical loading in 16 wk C3H mice (2210 με peak periosteal normal strain). Consistent with previous studies, none of the response measures were significantly elevated by a loading protocol previously found to be highly osteogenic in C57 mice.

Figure 2

Endocortical and periosteal (mean + SE) MS/BS (A), MAR (B) and BFR/BS (C) induced by rest-inserted loading in 16 wk C57 and 32 wk C3H mice. Peak periosteal normal strains were equivalent between groups. Response measures attaining significance are noted (*: p < 0.05, Loaded tibiae vs. non-loaded contralateral tibiae; †: p < 0.05, C3H vs. C57)

Figure 3

Endocortical and periosteal (mean ± SE) MS/BS (A), MAR (B) and BFR/BS (C) induced by cyclic mechanical loading of 32 wk C3H mice at peak periosteal strains of 1085 με (Low) and 1875 με (Moderate). Response measures attaining significance are noted (*: p < 0.05, Loaded tibiae vs. non-loaded contralateral tibiae; †: p < 0.05, C3H vs. C57)