Chen Yunxin, Klein-Nulend Jenneke, Bravenboer Nathalie
Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands.
Department of Laboratory Science, Amsterdam University Medical Centers (AUMC)/ Location VUmc, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
Curr Osteoporos Rep. 2025 Aug 12;23(1):35. doi: 10.1007/s11914-025-00927-0.
Bone matrix is a multiscale composite material mainly composed of collagen, crystalline apatite mineral, water, and a small amount of non-collagenous proteins. Nested within bone matrix, mechanosensitive osteocytes orchestrate bone adaptation to mechanical loading, which is affected by the ultrastructural composition and mechanical properties of the osteocyte-surrounding bone matrix. In this review, we shed light on the impact of ageing-related modifications in ultrastructural composition of bone matrix on the mechanosensitivity of osteocytes.
Ageing modulates the ultrastructural composition of bone matrix, such as collagen cross-links, mineral crystal size, microcracks, content of bound water, content and phosphorylation of non-collagenous proteins, and degree of mineralization. These ageing-related modifications alter the mechanical properties of bone matrix, and the biological function of bone, i.e. altered mechanical properties lead to changes in mechanical loading-induced fluid shear stress experienced by osteocytes, which affect osteocyte mechanosensitivity. A better understanding of the role of osteocyte mechanosensitivity in bone adaptation to mechanical loading during ageing is crucial. This review highlights the ageing-related changes in the ultrastructural composition and mechanical properties of bone matrix, that might affect the mechanosensitivity of osteocytes. By linking ageing-related changes in the bone matrix to alterations in osteocyte mechanosensitivity, it is assumed that ageing-modulated bone matrix affects bone adaptation to mechanical loading orchestrated by osteocytes. A comprehensive understanding of how age-related changes in bone matrix composition influence osteocyte mechanosensitivity is crucial for explaining the fragility of ageing bone, as osteocytes are the most abundant and mechanosensitive cells in bone tissue.
骨基质是一种多尺度复合材料，主要由胶原蛋白、结晶磷灰石矿物质、水和少量非胶原蛋白组成。机械敏感的骨细胞嵌套在骨基质中，协调骨骼对机械负荷的适应性，而这又受骨细胞周围骨基质的超微结构组成和力学性能影响。在本综述中，我们将阐明骨基质超微结构组成中与衰老相关的改变对骨细胞机械敏感性的影响。
衰老会调节骨基质的超微结构组成，如胶原蛋白交联、矿物晶体大小、微裂纹、结合水含量、非胶原蛋白含量及磷酸化水平以及矿化程度。这些与衰老相关的改变会改变骨基质的力学性能以及骨骼的生物学功能，即力学性能的改变会导致骨细胞所经历的机械负荷诱导的流体剪切应力发生变化，进而影响骨细胞的机械敏感性。深入了解骨细胞机械敏感性在衰老过程中骨骼对机械负荷适应中的作用至关重要。本综述强调了骨基质超微结构组成和力学性能中与衰老相关的变化，这些变化可能会影响骨细胞的机械敏感性。通过将骨基质中与衰老相关的变化与骨细胞机械敏感性的改变联系起来，可以推测衰老调节的骨基质会影响骨骼对骨细胞协调的机械负荷的适应性。全面了解骨基质组成的年龄相关变化如何影响骨细胞机械敏感性对于解释衰老骨骼的脆弱性至关重要，因为骨细胞是骨组织中数量最多且机械敏感的细胞。
