Akhter M P, Cullen D M, Pedersen E A, Kimmel D B, Recker R R
Osteoporosis Research Center, Creighton University, 601 North 30th Street 5766, Omaha, Nebraska 68131, USA.
Calcif Tissue Int. 1998 Nov;63(5):442-9. doi: 10.1007/s002239900554.
We investigated the bone response to external loading in C57BL/6J and C3H/HeJ mice, both breeds with low and high bone density, respectively. An in vivo tibial four-point bending device previously used for application of measured external loads in rats was adapted for mice. It delivered a uniform medio-lateral bending moment to the region of the tibia located 1-5.5 mm proximal to the tibio-fibula junction. The right legs of six C57BL/6J [low bone density (LBD)] and C3H/HeJ [high bone density (HBD)] mice were externally loaded in the device for 36 cycles/day at 2 Hz, 6 days/week for 2 weeks at 9.3 +/- 0.9 N force, inducing estimated lateral periosteal surface compressive strains of 5121 +/- 1128 mu epsilon in C3H/HeJ (HBD) mice (n = 6), significantly higher than the estimated 3988 +/- 820 mu epsilon in C57BL/6J mice (n = 6) (mean +/- SD). In addition, C3H/HeJ HBD mice (n = 11) were externally sham (pad pressure or no bending) loaded in the device for 36 cycles/day at 2 Hz, 3 days/week for 3 weeks at 9.3 +/- 0.9 N force. Calcein injections for bone labeling were given at the 10th and 3rd days before sacrifice. At the end of the experiment, all mice were killed and both tibiae were removed, fixed, embedded, and cross-sectioned through the loaded region. Both tibiae were measured for marrow area (Ma.Ar), cortical area (Ct.Ar), total area (Tt.Ar), cross-sectional moment of inertia (CSMI), and periosteal and endocortical woven bone surface (Wo.B/BS), single-labeled surface (sLS), double-labeled surface (dLS), and total formation surface (FS/BS). Differences in all variables due to breed and loading (both bending and sham-bending) were tested by two-way analysis of variance (ANOVA) (P < 0.05). Ma.Ar, Tt.Ar, and CSMI were greater in C57BL/6J (LBD) than in C3H/HeJ (HBD) mice. Periosteal and endocortical woven bone and formation surface were increased significantly more by loading (bending) in C57BL/6J than in C3H/HeJ mice. Periosteal woven bone response due to sham-bending or sham-loading was significantly lower than due to bending loads in the C3H/HeJ mice. We conclude that the bone response to external loading is greater in LBD mice than in HBD mice. The high bone density of C3H/HeJ (HBD) mice is related to breed-specific factors other than the response to loading.
我们研究了C57BL/6J和C3H/HeJ小鼠骨骼对外加载荷的反应，这两个品系小鼠的骨密度分别较低和较高。一种先前用于给大鼠施加测量的外加载荷的体内胫骨四点弯曲装置被改装用于小鼠。它向位于胫腓关节近端1 - 5.5毫米处的胫骨区域施加均匀的内外侧弯矩。6只C57BL/6J[低骨密度（LBD）]和C3H/HeJ[高骨密度（HBD）]小鼠的右腿在该装置中以2赫兹的频率每天进行36次循环加载，每周6天，持续2周，力为9.3±0.9牛，在C3H/HeJ（HBD）小鼠（n = 6）中诱导的外侧骨膜表面压缩应变估计为5121±1128微应变，显著高于C57BL/6J小鼠（n = 6）中估计的3988±820微应变（平均值±标准差）。此外，11只C3H/HeJ HBD小鼠在该装置中以2赫兹的频率每天进行36次循环假加载（垫压力或无弯曲），每周3天，持续3周，力为9.3±0.9牛。在处死前第10天和第3天进行钙黄绿素注射用于骨标记。实验结束时，所有小鼠均被处死，双侧胫骨被取出、固定、包埋，并通过加载区域进行横截面切片。测量双侧胫骨的骨髓面积（Ma.Ar）、皮质面积（Ct.Ar）、总面积（Tt.Ar）、截面惯性矩（CSMI）以及骨膜和皮质内编织骨表面（Wo.B/BS）、单标记表面（sLS）、双标记表面（dLS）和总形成表面（FS/BS）。通过双向方差分析（ANOVA）检验由于品系和加载（弯曲和假弯曲）导致的所有变量差异（P < 0.05）。C57BL/6J（LBD）小鼠的Ma.Ar、Tt.Ar和CSMI大于C3H/HeJ（HBD）小鼠。与C3H/HeJ小鼠相比，C57BL/6J小鼠通过加载（弯曲）使骨膜和皮质内编织骨以及形成表面的增加更为显著。在C3H/HeJ小鼠中，假弯曲或假加载引起的骨膜编织骨反应显著低于弯曲载荷引起的反应。我们得出结论，低骨密度小鼠骨骼对外加载荷的反应大于高骨密度小鼠。C3H/HeJ（HBD）小鼠的高骨密度与除加载反应之外的品系特异性因素有关。
