Lan Li, Jie Li, Jian-Jiang Li, Huan Zhou, Xing-Wang Zhu, Ping-Heng Zhang, Bo Huang, Wen-Ting Zhao, Xiao-Feng Zhao, En-Sheng Chen
{"title":"Chondrocyte autophagy mechanism and therapeutic prospects in osteoarthritis.","authors":"Lan Li, Jie Li, Jian-Jiang Li, Huan Zhou, Xing-Wang Zhu, Ping-Heng Zhang, Bo Huang, Wen-Ting Zhao, Xiao-Feng Zhao, En-Sheng Chen","doi":"10.3389/fcell.2024.1472613","DOIUrl":null,"url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most common type of arthritis characterized by progressive cartilage degradation, with its pathogenesis closely related to chondrocyte autophagy. Chondrocytes are the only cells in articular cartilage, and the function of chondrocytes plays a vital role in maintaining articular cartilage homeostasis. Autophagy, an intracellular degradation system that regulates energy metabolism in cells, plays an incredibly important role in OA. During the early stages of OA, autophagy is enhanced in chondrocytes, acting as an adaptive mechanism to protect them from various environmental changes. However, with the progress of OA, chondrocyte autophagy gradually decreases, leading to the accumulation of damaged organelles and macromolecules within the cell, prompting chondrocyte apoptosis. Numerous studies have shown that cartilage degradation is influenced by the senescence and apoptosis of chondrocytes, which are associated with reduced autophagy. The relationship between autophagy, senescence, and apoptosis is complex. While autophagy is generally believed to inhibit cellular senescence and apoptosis to promote cell survival, recent studies have shown that some proteins are degraded by selective autophagy, leading to the secretion of the senescence-associated secretory phenotype (SASP) or increased SA-β-Gal activity in senescent cells within the damaged region of human OA cartilage. Autophagy activation may lead to different outcomes depending on the timing, duration, or type of its activation. Thus, our study explored the complex relationship between chondrocyte autophagy and OA, as well as the related regulatory molecules and signaling pathways, providing new insights for the future development of safe and effective drugs targeting chondrocyte autophagy to improve OA.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537998/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cell and Developmental Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fcell.2024.1472613","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Osteoarthritis (OA) is the most common type of arthritis characterized by progressive cartilage degradation, with its pathogenesis closely related to chondrocyte autophagy. Chondrocytes are the only cells in articular cartilage, and the function of chondrocytes plays a vital role in maintaining articular cartilage homeostasis. Autophagy, an intracellular degradation system that regulates energy metabolism in cells, plays an incredibly important role in OA. During the early stages of OA, autophagy is enhanced in chondrocytes, acting as an adaptive mechanism to protect them from various environmental changes. However, with the progress of OA, chondrocyte autophagy gradually decreases, leading to the accumulation of damaged organelles and macromolecules within the cell, prompting chondrocyte apoptosis. Numerous studies have shown that cartilage degradation is influenced by the senescence and apoptosis of chondrocytes, which are associated with reduced autophagy. The relationship between autophagy, senescence, and apoptosis is complex. While autophagy is generally believed to inhibit cellular senescence and apoptosis to promote cell survival, recent studies have shown that some proteins are degraded by selective autophagy, leading to the secretion of the senescence-associated secretory phenotype (SASP) or increased SA-β-Gal activity in senescent cells within the damaged region of human OA cartilage. Autophagy activation may lead to different outcomes depending on the timing, duration, or type of its activation. Thus, our study explored the complex relationship between chondrocyte autophagy and OA, as well as the related regulatory molecules and signaling pathways, providing new insights for the future development of safe and effective drugs targeting chondrocyte autophagy to improve OA.
骨关节炎(OA)是最常见的关节炎类型,以软骨进行性退化为特征,其发病机制与软骨细胞自噬密切相关。软骨细胞是关节软骨中唯一的细胞,软骨细胞的功能对维持关节软骨的平衡起着至关重要的作用。自噬是一种调节细胞能量代谢的细胞内降解系统,在 OA 中发挥着极其重要的作用。在 OA 的早期阶段,软骨细胞中的自噬作用增强,这是一种保护软骨细胞免受各种环境变化影响的适应机制。然而,随着 OA 的进展,软骨细胞的自噬作用逐渐减弱,导致细胞内受损细胞器和大分子的积累,促使软骨细胞凋亡。大量研究表明,软骨降解受软骨细胞衰老和凋亡的影响,而软骨细胞衰老和凋亡与自噬减少有关。自噬、衰老和凋亡之间的关系非常复杂。虽然自噬通常被认为能抑制细胞衰老和凋亡以促进细胞存活,但最近的研究表明,一些蛋白质会被选择性自噬降解,导致衰老相关分泌表型(SASP)的分泌或人类OA软骨受损区域内衰老细胞的SA-β-Gal活性增加。自噬激活的时间、持续时间或类型不同,可能导致不同的结果。因此,我们的研究探讨了软骨细胞自噬与OA之间的复杂关系,以及相关的调控分子和信号通路,为将来开发针对软骨细胞自噬的安全有效的药物以改善OA提供了新的见解。
期刊介绍:
Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board.
The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology.
With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.