Poliachik Sandra L, Threet DeWayne, Srinivasan Sundar, Gross Ted S
Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA, 98104, USA.
Bone. 2008 Apr;42(4):653-9. doi: 10.1016/j.bone.2007.12.222. Epub 2008 Jan 15.
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.
大量研究表明,与C57BL/6J(C57)小鼠相比,C3H/HeJ(C3H)小鼠对机械负荷的反应较为轻微。基于表明16周龄C3H小鼠骨膜成骨细胞具有较高基线活性的数据,我们推测,只需让C3H小鼠老化至其基础骨膜骨形成与16周龄C57小鼠相当,就能恢复C3H小鼠的机械反应性。我们通过对32周龄C3H小鼠和16周龄C57小鼠的右胫骨施加低强度间歇加载(峰值应变:1235με),然后对32周龄C3H小鼠的右胫骨施加低强度(1085με)或中等强度(1875με)的循环加载,来验证这一假设。通过动态组织形态计量学评估皮质内和骨膜表面对加载的成骨细胞反应。在32周龄时,与未加载的对侧骨骼相比,C3H小鼠对低强度间歇加载的反应是骨膜矿化表面、矿物质沉积率和骨形成显著升高。令人惊讶的是,低强度间歇加载在C3H小鼠中诱导的骨膜骨形成超过了16周龄C57小鼠中诱导的骨膜骨形成。在32周龄时,C3H小鼠对增加的循环加载强度也表现出增强的反应。我们得出结论,16周龄C3H小鼠中高水平的基础成骨细胞功能似乎超过了组织对原本合成代谢性机械负荷刺激的反应能力。然而,当基础表面成骨细胞活性与16周龄C57小鼠相当时,C3H小鼠表现出对间歇加载或循环加载的明显反应能力。