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Updated: Jun 29, 2025
Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
Senescent-like macrophages mediate angiogenesis for endplate sclerosis via IL-10 secretion in male mice
Yonggang Fan1, Weixin Zhang2, Xiusheng Huang1
1Department of Orthopaedics, 1st Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, PR China.
Abstract:
Endplate sclerosis is a notable aspect of spine degeneration or aging, but the mechanisms remain unclear. Here, we report that senescent macrophages accumulate in the sclerotic endplates of lumbar spine instability (LSI) or aging male mouse model. Specifically, knockout of cdkn2a (p16) in macrophages abrogates LSI or aging-induced angiogenesis and sclerosis in the endplates. Furthermore, both in vivo and in vitro studies indicate that IL-10 is the primary elevated cytokine of senescence-related secretory phenotype (SASP). Mechanistically, IL-10 increases pSTAT3 in endothelial cells, leading to pSTAT3 directly binding to the promoters of Vegfa, Mmp2, and Pdgfb to encourage their production, resulting in angiogenesis. This study provides information on understanding the link between immune senescence and endplate sclerosis, which might be useful for therapeutic approaches.
Insights
Senescent macrophages drive spine degeneration by promoting angiogenesis and sclerosis via IL-10. Blocking p16 in macrophages prevents these changes, offering therapeutic insights for endplate sclerosis.
Area of Science:
- Immunology
- Gerontology
- Orthopedics
Background:
- Endplate sclerosis is a common feature of spinal degeneration and aging.
- The underlying mechanisms of endplate sclerosis are not fully understood.
Purpose of the Study:
- To investigate the role of senescent macrophages in endplate sclerosis.
- To elucidate the molecular mechanisms linking immune senescence to spinal degeneration.
Main Methods:
- Utilized a male mouse model of lumbar spine instability (LSI) or aging.
- Generated macrophage-specific cdkn2a (p16) knockout mice.
- Performed in vivo and in vitro studies to analyze cytokine profiles and cellular signaling pathways.
Main Results:
- Senescent macrophages accumulate in sclerotic endplates of aging/LSI mice.
- Macrophage p16 knockout inhibited LSI/aging-induced angiogenesis and sclerosis.
- Interleukin-10 (IL-10) was identified as a key elevated cytokine in senescence-related secretory phenotype (SASP).
- IL-10 signaling via pSTAT3 in endothelial cells promoted the expression of Vegfa, Mmp2, and Pdgfb, driving angiogenesis.
Conclusions:
- Immune senescence, specifically via macrophages, contributes to endplate sclerosis.
- The IL-10/pSTAT3/VEGF pathway is crucial for angiogenesis in endplate degeneration.
- Targeting macrophage senescence may offer novel therapeutic strategies for endplate sclerosis.
