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雷氏方通过抑制 mTOR 轴介导的软骨细胞衰老减轻骨关节炎:体内和体外实验。

Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: and experiments.

机构信息

The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

Alberta Institute, Wenzhou Medical University, Wenzhou, Zhejiang, China.

出版信息

Aging (Albany NY). 2024 Feb 23;16(5):4250-4269. doi: 10.18632/aging.205582.

DOI:10.18632/aging.205582
PMID:38407978
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10968702/
Abstract

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). findings demonstrate that LSF shields chondrocytes from HO-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

摘要

雷氏方剂(LSF)是一种传统的中草药疗法,因其在治疗骨关节炎(OA)方面的显著临床疗效而受到认可。尽管它具有治疗潜力,但 LSF 在 OA 中的作用的确切分子机制仍然是个谜。现有研究已经揭示了 mTOR 信号通路在促进软骨细胞衰老中的作用,而软骨细胞衰老正是 OA 相关软骨退化的一个核心因素。因此,靶向 mTOR 以减轻软骨细胞衰老为 OA 治疗提供了一个有前途的途径。本研究的主要目的是通过抑制 mTOR 来确定 LSF 的软骨保护潜力及其抗骨关节炎的疗效。OA 小鼠模型的评估显示出明显的关节软骨退化。然而,LSF 是关节软骨的有效保护者,其表现为:骨硬化减少、软骨厚度增加、表面光滑度提高、OARSI 评分降低、软骨合成标志物(Col2 和 Aggrecan)表达升高、软骨分解标志物(Adamts5 和 MMP13)表达降低、软骨细胞肥大标志物(Col10)表达增加以及软骨细胞衰老标志物(P16 和 P21)表达降低。这些发现表明,LSF 可以保护软骨细胞免受 HO 诱导的凋亡,抑制衰老,增强软骨细胞分化,促进 II 型胶原和蛋白聚糖的合成,减少软骨降解。从机制上讲,LSF 通过 mTOR 轴抑制软骨细胞衰老,调节软骨细胞合成代谢与分解代谢的平衡,最终减少凋亡并减缓 OA 软骨降解。LSF 作为 OA 治疗的一种治疗方法具有重要意义,为这种常见的与年龄相关的疾病的潜在治疗方法提供了新的见解。

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