胶原纤维在骨骼多尺度力学行为和力学响应增龄性变化中的作用

The collagen network in bone formed by collagen is the basic scaffold for mineralization. The collagen network plays a decisive role for bone to establish the unique hierarchical structure and mechanical behaviour. Aging is a physiological process including growth, maturity and caducity. Ageing causes the alterations on the mechanical behaviour and mechano-adaptive response of bone. Our previous studies found that the elastic deformation of bone is characterized by the elongation of the collagen fibrils and the sliding between the fibrils. The elastic modulus of the collagen fibrils in the murine tibia was reduced by disuse. The orientation of the collagen fibrils in disused bone was altered during load bearing. It is therefore indicated that the collagen fibrils is crucial for the mechanical behaviour and mechanical-response of bone. However, how the collagen fibrils contribute to the changes of bone due to aging remains unknown..Utilizing the scanning and nano-indentation approaches based on Atomic Force Microscopy, the present proposal intends to investigate: ①The influence of aging on the structure, orientation and in situ mechanical properties of the collagen fibrils; ②The role of the collagen fibrils in the response of aging bone to mechanical disuse and mechanical stimulation. ③The relationship between the mechanical behaviour of bone at different scales under physiological loading, and how aging influences such a relationship. It is expected that the role of the collagen fibrils during the alterations of mechanical behaviour and mechanical response of bone induced by aging can be identified with the present proposal. Moreover, it is expected that new ideas could be proposed on the treatment of the osteoporosis caused by aging.

胶原蛋白形成的纤维网状结构是骨矿物质沉积的基本骨架，其对骨形成独特的层级结构和多尺度力学性能至关重要。增龄是机体生长、成熟和衰老的生理过程，骨骼的力学行为和对力学刺激的响应随该过程发生改变。申请者研究发现胶原纤维轴向拉伸和相对滑动是骨在弹性形变阶段的主要特征；尾悬吊后肢废用导致成年小鼠胫骨胶原纤维原位弹性模量降低，受力形变时纤维排布散乱，提示胶原纤维在骨力学行为和响应力学刺激时的重要作用，然而，胶原纤维影响骨增龄性变化过程的规律尚不清楚。.本项目拟利用原子力显微镜扫描及纳米压痕测试技术，研究：①增龄过程中骨胶原纤维结构、排布和原位力学性能的变化；②生理载荷条件下，骨骼多尺度力学行为之间的关系，以及增龄对该关系的影响；③胶原纤维在不同年龄的骨骼响应肌骨废用和力学刺激过程中的作用规律。揭示胶原纤维在骨骼不同尺度增龄性变化中的作用，为防治增龄导致的骨质疏松等退行性疾病提供新的思路。

骨是由无机矿物质和胶原等蛋白分子按照一定的层级结构排列组成的复合物。胶原蛋白和骨矿物质共同决定骨的力学性能。骨胶原蛋白形成的纤维网状结构是矿物质沉积的基本骨架，其对骨形成多尺度层级结构和独特的力学行为至关重要。增龄是机体生长、成熟和衰老的生理过程，该过程导致骨的力学行为和对力学刺激的响应发生改变。申请者研究发现胶原纤维轴向拉伸和相对滑动是骨在弹性形变阶段的主要特征；尾悬吊后肢废用导致成年小鼠胫骨胶原纤维原位弹性模量降低，受力形变时纤维排布散乱，提示胶原纤维在骨力学行为和响应力学刺激时的重要作用，然而，胶原纤维影响骨增龄性变化过程的规律尚不清楚。.本项目利用原子力显微镜扫描及压痕技术，研究了骨在增龄过程中胶原纤维的结构、排布和原位力学性能的变化，以及骨胶原纤维在不同年龄的骨响应肌骨废用过程中的作用规律。本研究研制了基于原子力显微镜的原位骨力学加载实验平台、构建了增龄动物模型，利用纳米压痕仪、拉曼光谱等技术，在多个尺度研究了小鼠胫骨皮质骨力学性能、微观结构和组成成分的增龄性变化。结果表明，增龄以及通常伴随增龄的肌骨费用导致的骨变化始于骨基质中的矿化胶原纤维。老龄鼠皮质骨表面矿化胶原纤维的横纹周期、单根矿化胶原纤维的径向弹性模量和矿物基质比均大于成年鼠。老龄鼠胫骨皮质骨矿化胶原纤维的形态和力学性能对肌骨废用更为敏感，但成年鼠骨则对肌骨废用不敏感。这些发现揭示了骨矿化胶原纤维增龄和废用过程中的组成成分、结构变化和力学适应性的变化。本项目的研究为理解增龄和肌骨废用对骨不同尺度的结构和力学性能调节机制，以及骨在宏观至微观尺度对年龄和力学环境的适应过程提供数据和理论支持，为预防增龄导致的骨质疏松等退行性疾病提供新的思路。