Dept. of Health and Kinesiology, MS 4243, Texas A&M Univ., College Station, TX 77843-4243, USA.
J Appl Physiol (1985). 2012 Mar;112(5):918-25. doi: 10.1152/japplphysiol.00978.2011. Epub 2011 Dec 15.
Mechanical loading modulates the osteocyte-derived protein sclerostin, a potent inhibitor of bone formation. We hypothesized that simulated resistance training (SRT), combined with alendronate (ALEN) treatment, during hindlimb unloading (HU) would most effectively mitigate disuse-induced decrements in cortical bone geometry and formation rate (BFR). Sixty male, Sprague-Dawley rats (6-mo-old) were randomly assigned to either cage control (CC), HU, HU plus either ALEN (HU+ALEN), or SRT (HU+SRT), or combined ALEN and SRT (HU+SRT/ALEN) for 28 days. Computed tomography scans on days -1 and 28 were taken at the middiaphyseal tibia. HU+SRT and HU+SRT/ALEN rats were subjected to muscle contractions once every 3 days during HU (4 sets of 5 repetitions; 1,000 ms isometric + 1,000 ms eccentric). The HU+ALEN and HU+SRT/ALEN rats received 10 μg/kg ALEN 3 times/wk. Compared with the CC animals, HU suppressed the normal slow growth-induced increases of cortical bone mineral content, cortical bone area, and polar cross-sectional moment of inertia; however, SRT during HU restored cortical bone growth. HU suppressed middiaphyseal tibia periosteal BFR by 56% vs. CC (P < 0.05). However, SRT during HU restored BFR at both periosteal (to 2.6-fold higher than CC) and endocortical (14-fold higher than CC) surfaces (P < 0.01). ALEN attenuated the SRT-induced BFR gains during HU. The proportion of sclerostin-positive osteocytes in cortical bone was significantly higher (+121% vs. CC) in the HU group; SRT during HU effectively suppressed the higher proportion of sclerostin-positive osteocytes. In conclusion, a minimum number of high-intensity muscle contractions, performed during disuse, restores cortical BFR and suppress unloading-induced increases in sclerostin-positive osteocytes.
机械负荷调节骨细胞来源的蛋白硬化素（sclerostin），这是一种骨形成的强力抑制剂。我们假设，在下肢去负荷（hindlimb unloading，HU）期间进行模拟抗阻训练（simulated resistance training，SRT）并联合阿仑膦酸钠（alendronate，ALEN）治疗，将最有效地减轻废用引起的皮质骨几何形状和形成率（bone formation rate，BFR）的下降。60 只雄性 Sprague-Dawley 大鼠（6 月龄）被随机分为笼养对照（cage control，CC）、HU、HU 加阿仑膦酸钠（HU+ALEN）、SRT（HU+SRT）或 SRT 联合阿仑膦酸钠（HU+SRT/ALEN）组，进行 28 天治疗。在第-1 天和第 28 天对胫骨中段进行计算机断层扫描。HU 期间，HU+SRT 和 HU+SRT/ALEN 大鼠每 3 天接受一次肌肉收缩（4 组，每组 5 次重复；1000 ms 等长+1000 ms 离心）。HU+ALEN 和 HU+SRT/ALEN 大鼠每周接受 3 次 10 μg/kg 的阿仑膦酸钠。与 CC 动物相比，HU 抑制了皮质骨矿物质含量、皮质骨面积和极惯性矩的正常缓慢生长诱导增加；然而，HU 期间的 SRT 恢复了皮质骨生长。HU 抑制了胫骨中段皮质骨的骨形成率（periosteal bone formation rate，BFR），与 CC 相比降低了 56%（P < 0.05）。然而，HU 期间的 SRT 恢复了皮质骨内外表面的 BFR（骨内膜 BFR 增加了 14 倍，高于 CC；骨外膜 BFR 增加了 2.6 倍，高于 CC）（P < 0.01）。ALEN 减弱了 HU 期间 SRT 引起的 BFR 增加。HU 组皮质骨中硬化素阳性骨细胞的比例显著升高（与 CC 相比增加了 121%）；HU 期间的 SRT 有效抑制了硬化素阳性骨细胞的比例增加。总之，在废用期间进行的高强度肌肉收缩次数最少，可以恢复皮质骨 BFR，并抑制去负荷引起的硬化素阳性骨细胞增加。
