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Abstract：
Senescence is a complex cell state characterized by stable cell cycle arrest and a unique secretory pattern known as the senescence-associated secretory phenotype (SASP). The SASP factors, which are heterogeneous and tissue specific, normally include chemokines, cytokines, growth factors, adhesion molecules, and lipid components that can lead to multiple age-associated disorders by eliciting local and systemic consequences. The skeleton is a highly dynamic organ that changes constantly in shape and composition. Senescent cells in bone and bone marrow produce diverse SASP factors that induce alterations of the skeleton through paracrine effects. Herein, we refer to bone cell-associated SASP as \"bone-SASP.\" In this review, we describe current knowledge of cellular senescence and SASP, focusing on the role of senescent cells in mediating bone pathologies during natural aging and premature aging syndromes. We also summarize the role of cellular senescence and the bone-SASP in glucocorticoids-induced bone damage. In addition, we discuss the role of bone-SASP in the development of osteoarthritis, highlighting the mechanisms by which bone-SASP drives subchondral bone changes in metabolic syndrome-associated osteoarthritis.
摘要：
衰老是一种复杂的细胞状态，其特征是稳定的细胞周期停滞和独特的分泌模式，称为衰老相关分泌表型（SASP）。SASP因素，它们是异质的和组织特异性的，通常包括趋化因子，细胞因子,生长因子，粘附分子,和脂质成分，可通过引发局部和全身后果而导致多种与年龄相关的疾病。骨骼是一种高度动态的器官，其形状和组成不断变化。骨骼和骨髓中的衰老细胞产生多种SASP因子，这些SASP因子通过旁分泌效应诱导骨骼的改变。在这里，我们将与骨细胞相关的SASP称为“骨SASP”。“在这次审查中，我们描述了细胞衰老和SASP的最新知识，重点研究衰老细胞在自然衰老和过早衰老综合征中介导骨病变的作用。我们还总结了细胞衰老和骨SASP在糖皮质激素诱导的骨损伤中的作用。此外,我们讨论了骨SASP在骨关节炎发展中的作用，强调骨SASP驱动代谢综合征相关骨关节炎软骨下骨变化的机制。
