Osthole Suppresses Knee Osteoarthritis Development by Enhancing Autophagy Activated via the AMPK/ULK1 Pathway

Ma, Teng; Wang, Xiangpeng; Qu, Wentao; Yang, Lingsen; Cheng, Jiang; Zhu, Bingrui; Zhang, Yongkui; Xie, Wen‐Peng

doi:10.3390/molecules27238624

Cited by 5 publications

(2 citation statements)

References 45 publications

(48 reference statements)

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“…Furthermore, osthol, an active chemical ingredient in LSF, has been identified to reduce oxidative stress damage to chondrocytes and delay cellular senescence. These findings align with our previous clinical observations demonstrating LSF’s ability to improve osteoarthritis symptoms [ 31 , 32 ]. However, the specific pathological mechanism by which LSF acts on OA remains unclear.…”

Section: Introductionsupporting

confidence: 92%

“…Therefore, there is a pressing need to explore more potent drugs to effectively treat OA. Lei’s formula (LSF), an integral component of traditional Chinese medicine, incorporates Duhuo-Qianghuo pair and a variety of effective chemical components, including Osthole and Notopterol [ 24 – 26 , 28 , 32 , 40 ]. Previous studies have confirmed its anti-inflammatory and antioxidative properties, making it a promising candidate for OA treatment.…”

Section: Discussionmentioning

confidence: 99%

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Lei’s formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments

Zhou,

Li,

Zhuang

et al. 2024

Aging

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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. In vivo 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). In vitro findings demonstrate that LSF shields chondrocytes from H 2 O 2 -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.

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Section: Introductionsupporting

confidence: 92%