PDF(Pubmed)
Abstract：
Fragility fractures, which are more prevalent in women, may be significantly influenced by autophagy due to altered bone turnover. As an essential mediator of autophagy, Beclin-1 modulates bone homeostasis by regulating osteoclast and chondrocyte differentiation, however, the alteration in the local bone mechanical environment in female Beclin-1+/- mice remains unclear. In this study, our aim is to investigate the biomechanical behavior of femurs from seven-month-old female wild-type (WT) and Beclin-1+/- mice under peak physiological load, using finite element analysis on micro-CT images. Micro-CT imaging analyses revealed femoral cortical thickening in Beclin-1+/- female mice compared to WT. Three-point bending test demonstrated a 63.94% increase in whole-bone strength and a 61.18% increase in stiffness for female Beclin-1+/- murine femurs, indicating improved biomechanical integrity. After conducting finite element analysis, Beclin-1+/- mice exhibited a 26.99% reduction in von Mises stress and a 31.62% reduction in maximum principal strain in the femoral midshaft, as well as a 36.64% decrease of von Mises stress in the distal femurs, compared to WT mice. Subsequently, the strength-safety factor was determined using an empirical formula, revealing that Beclin-1+/- mice exhibited significantly higher minimum safety factors in both the midshaft and distal regions compared to WT mice. In summary, considering the increased response of bone adaptation to mechanical loading in female Beclin-1+/- mice, our findings indicate that increasing cortical bone thickness significantly improves bone biomechanical behavior by effectively reducing stress and strain within the femoral shaft.
摘要：
脆性骨折,这在女性中更为普遍，由于骨转换改变，自噬可能会受到显着影响。作为自噬的重要介质，Beclin-1通过调节破骨细胞和软骨细胞分化来调节骨稳态，然而,雌性Beclin-1+/-小鼠局部骨机械环境的改变尚不清楚。在这项研究中,我们的目的是研究从7个月大的雌性野生型（WT）和Beclin-1+/-小鼠的股骨在峰值生理负荷下的生物力学行为，对显微CT图像进行有限元分析。Micro-CT成像分析显示，与WT相比，Beclin-1/-雌性小鼠的股骨皮质增厚。三点弯曲测试表明，雌性Beclin-1+/-鼠股骨的全骨强度增加了63.94%，刚度增加了61.18%，表明生物力学完整性得到改善。进行有限元分析后,Beclin-1+/-小鼠表现出26.99%的vonMises应力减少和31.62%的最大主应变在股骨中段，以及股骨远端vonMises应力下降36.64%，与WT小鼠相比。随后，强度安全系数是用经验公式确定的，与WT小鼠相比，Beclin-1+/-小鼠在中段和远端区域表现出明显更高的最小安全系数。总之,考虑到雌性Beclin-1+/-小鼠的骨适应对机械负荷的反应增加，我们的研究结果表明,增加皮质骨厚度可有效降低股骨干内的应力和应变,从而显著改善骨生物力学行为.
