Osx1-Cre靶向细胞中的自噬对于骨骼的发育、生长和维持至关重要
Autophagy in Osx1-Cre-targeted cells is essential for development, growth, and maintenance of bone.
摘要(中文译文)
自噬是一种细胞回收途径，其中细胞质成分被递送至溶酶体进行降解。自噬水平的变化已被认为与多种骨骼病理相关，包括骨质疏松症。在成骨细胞谱系的不同阶段消除自噬会减少骨形成和骨量。然而，自噬是否在骨骼的发育、生长或维持过程中发挥特定作用仍不清楚。为开始解答这一问题，我们在产前或断奶时消除了整个成骨细胞谱系中的自噬，并在4.5月龄和10月龄时对小鼠进行骨骼表型分析。我们发现，无论何时从成骨细胞谱系中消除自噬，自噬缺陷均会降低股骨和脊柱的骨密度（BMD）、皮质厚度和松质骨体积。系列BMD分析显示，自噬缺陷小鼠在3至9月龄期间BMD持续较低，且基因型之间的BMD差异在脊柱中逐渐增大。自噬缺陷小鼠椎体松质骨体积的减少与骨形成减少相关。为评估自噬诱导的细胞和分子水平变化，我们对骨膜间充质细胞进行了单细胞RNA测序（scRNA-seq）分析，并比较了骨膜和骨内膜细胞制备物中自噬缺陷诱导的变化。该分析揭示，自噬缺陷会破坏蛋白质稳态，引起线粒体功能障碍，诱导衰老，并增加如TNF和TGF-β等应激反应通路。总体而言，我们得出结论：自噬对骨骼生长和骨维持具有重要作用，并确定了自噬支持骨形成所经由的潜在细胞群体和细胞过程。
Abstract
Autophagy is a cellular recycling pathway in which cytoplasmic components are delivered to lysosomes for degradation. Changes in autophagy levels have been implicated in various skeletal pathologies including osteoporosis. Elimination of autophagy at different stages of the osteoblast lineage reduces bone formation and bone mass. However, whether autophagy plays a role specifically during development, growth, or maintenance of bone remains unclear. To start addressing this question, we eliminated autophagy in the entire osteoblast lineage prenatally or at weaning and subjected the mice to skeletal phenotyping at 4.5 and 10 months of age. We found that regardless of when autophagy was eliminated from the osteoblast lineage, autophagy deficiency reduced bone mineral density (BMD), cortical thickness, and cancellous bone volume in the femur and spine. Serial BMD analysis revealed that autophagy-deficient mice had consistently lower BMDs from 3 to 9 months of age, and the BMD difference between genotypes became progressively greater in the spine. The reduction in vertebral cancellous bone volume of autophagy-deficient mice was associated with reduced bone formation. To assess autophagy-induced changes at the cellular and molecular level, we performed single-cell RNA-sequencing (scRNA-seq) analysis of periosteal mesenchymal cells and compared autophagy deficiency-induced changes in periosteal and endosteal cell preparations. This analysis revealed that autophagy deficiency disrupts proteostasis, causes mitochondrial dysfunction, induces senescence, and increases stress response pathways like TNF and TGF-β. Overall, we conclude that autophagy is important for skeletal growth and maintenance of bone, and we identify potential cellular populations and cellular processes via which autophagy support bone formation.
如何引用
AMA
Alicen James, Ilham Kadhim, Jacob Laster, Vivek Khanal, Jeff Thostenson, Neha Dole, et al. Autophagy in Osx1-Cre-targeted cells is essential for development, growth, and maintenance of bone.. Bone reports. 2026; doi:10.1016/j.bonr.2026.101941.
APA
Alicen James, Ilham Kadhim, Jacob Laster, Vivek Khanal, Jeff Thostenson, Neha Dole, et al (2026). Autophagy in Osx1-Cre-targeted cells is essential for development, growth, and maintenance of bone.. Bone reports. https://doi.org/10.1016/j.bonr.2026.101941
GB/T 7714
Alicen James, Ilham Kadhim, Jacob Laster, Vivek Khanal, Jeff Thostenson, Neha Dole, et al. Autophagy in Osx1-Cre-targeted cells is essential for development, growth, and maintenance of bone.[J]. Bone reports, 2026 doi:10.1016/j.bonr.2026.101941.
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