PDF(Pubmed)
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.
摘要：
终板硬化是脊柱退化或老化的一个值得注意的方面，但机制尚不清楚。这里,我们报告说，衰老的巨噬细胞在腰椎不稳定（LSI）或衰老的雄性小鼠模型的硬化终板中积累。具体来说,巨噬细胞中cdkn2a（p16）的敲除消除了LSI或老化诱导的终板中的血管生成和硬化。此外，体内和体外研究均表明，IL-10是衰老相关分泌表型（SASP）的主要升高细胞因子。机械上,IL-10增加内皮细胞中的pSTAT3，导致pSTAT3直接与Vegfa的启动子结合，Mmp2和Pdgfb鼓励他们的生产，导致血管生成。这项研究提供了有关了解免疫衰老与终板硬化之间联系的信息，这可能对治疗方法有用。
