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衰老会损害破骨细胞对胶原蛋白完整性和骨质量的调节作用。

Aging impairs the osteocytic regulation of collagen integrity and bone quality.

机构信息

Department of Orthopaedic Surgery, University of California, San Francisco, CA, 94143, USA.

UC Berkeley/UCSF Graduate Program in Bioengineering, San Francisco, CA, 94143, USA.

出版信息

Bone Res. 2024 Feb 26;12(1):13. doi: 10.1038/s41413-023-00303-7.

DOI:10.1038/s41413-023-00303-7
PMID:38409111
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10897167/
Abstract

Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβ signaling (TβRII) that suppresses PLR. The control aged bone displayed decreased TGFβ signaling and PLR, but aging did not worsen the existing PLR suppression in male TβRII bone. This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests. The effects of age on bone mass, density, and mineral material behavior were independent of osteocytic TGFβ. We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

摘要

骨质量差是老年人骨骼脆弱的一个主要因素。独立于骨量而建立和维持骨质量的分子机制尚不清楚，但据认为主要由骨细胞决定。我们假设，与年龄相关的骨质量下降是由于破骨细胞陷窝/管腔重塑 (PLR) 的抑制，而 PLR 维持着骨材料特性。我们研究了具有骨细胞内在 TGFβ 信号转导 (TβRII) 抑制的年轻和老年小鼠的骨骼，这种抑制抑制了 PLR。对照老年骨显示 TGFβ 信号和 PLR 降低，但在雄性 TβRII 骨中，衰老并没有使现有的 PLR 抑制恶化。这种关系影响了宏观机械测试中胶原材料的纳米和组织尺度的行为。年龄对骨量、密度和矿物质材料行为的影响与骨细胞 TGFβ 无关。我们确定，随着年龄的增长，骨质量的下降源于骨细胞功能的丧失和 TGFβ 依赖性胶原完整性维持的丧失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/6ab3f9fccdcf/41413_2023_303_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/ea9df14c90c9/41413_2023_303_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/18ea35576621/41413_2023_303_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/9e4ec80b86af/41413_2023_303_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/761518e86611/41413_2023_303_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/4e2220709b69/41413_2023_303_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/6ab3f9fccdcf/41413_2023_303_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/ea9df14c90c9/41413_2023_303_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/18ea35576621/41413_2023_303_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/3e186d8b048a/41413_2023_303_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/9e4ec80b86af/41413_2023_303_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/761518e86611/41413_2023_303_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/4e2220709b69/41413_2023_303_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce2a/10897167/6ab3f9fccdcf/41413_2023_303_Fig7_HTML.jpg

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