Silva Matthew J, Brodt Michael D
Department of Orthopedic Surgery, Washington University School of Medicine, 1 Barnes-Jewish Hospital Plaza, Suite 11300 WP, St. Louis, MO 63110, USA.
Calcif Tissue Int. 2008 Jun;82(6):489-97. doi: 10.1007/s00223-008-9142-5.
With aging, the skeleton may have diminished responsiveness to mechanical stimulation. The senescence-accelerated mouse SAMP6 has many features of senile osteoporosis and is thus a useful model to examine how the osteoporotic skeleton responds to mechanical loading. We performed in vivo tibial bending on 4-month-old SAMP6 (osteoporotic) and SAMR1 (control) mice. Loading was applied daily (60 cycles/day, 5 days/week) for 2 weeks at peak force levels that produced estimated endocortical strains of 1,000 and 2,000 microepsilon In a separate group of mice, sham bending was applied. Comparisons were made between right (loaded) and left (nonloaded) tibiae. Tibial bone marrow cells were cultured under osteogenic conditions and stained for alkaline phosphatase (ALP) and alizarin red (ALIZ) at 14 and 28 days, respectively. Tibiae were then embedded in plastic and sectioned, and endocortical bone formation was assessed based on calcein labels. Tibial bending did not alter the osteogenic potential of the marrow as there were no significant differences in ALP or ALIZ staining between loaded and nonloaded bones. Tibial bending activated the formation of endocortical bone in both SAMP6 and SAMR1 mice, whereas sham bending did not elicit an endocortical response. Both groups of mice exhibited bending strain-dependent increases in bone formation rate. We found little evidence of diminished responsiveness to loading in the SAMP6 skeleton. In conclusion, the ability of the SAMP6 mouse to respond normally to an anabolic mechanical stimulus distinguishes it from chronologically aged animals. This finding highlights a limitation of the SAMP6 mouse as a model of senile osteoporosis.
随着年龄增长，骨骼对机械刺激的反应可能会减弱。衰老加速小鼠SAMP6具有许多老年性骨质疏松的特征，因此是研究骨质疏松骨骼如何对机械负荷作出反应的有用模型。我们对4个月大的SAMP6（骨质疏松）小鼠和SAMR1（对照）小鼠进行了体内胫骨弯曲实验。每天施加负荷（60次循环/天，5天/周），持续2周，峰值力水平产生的估计皮质内应变分别为1000和2000微应变。在另一组小鼠中，施加假弯曲。对右侧（加载）和左侧（未加载）胫骨进行比较。将胫骨骨髓细胞在成骨条件下培养，并分别在第14天和第28天进行碱性磷酸酶（ALP）和茜素红（ALIZ）染色。然后将胫骨嵌入塑料中并切片，根据钙黄绿素标记评估皮质内骨形成。胫骨弯曲并未改变骨髓的成骨潜能，因为加载和未加载骨骼之间的ALP或ALIZ染色没有显著差异。胫骨弯曲激活了SAMP6和SAMR1小鼠皮质内骨的形成，而假弯曲未引发皮质内反应。两组小鼠均表现出弯曲应变依赖性的骨形成率增加。我们几乎没有发现SAMP6骨骼对负荷反应性降低的证据。总之，SAMP6小鼠对合成代谢机械刺激正常反应的能力使其有别于按时间顺序衰老的动物。这一发现凸显了SAMP6小鼠作为老年性骨质疏松模型的局限性。
