Dendrobine Alleviates Cellular Senescence and Osteoarthritis via the ROS/NF-κB Axis

Abstract

Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and cartilage degradation. Dendrobine (DEN) is reported to inhibit inflammation and oxidative stress in some diseases, but its role in chondrocyte senescence and OA progress has not yet been elucidated. Our study aimed to explore the protective effects of DEN on OA both in vitro and in vivo. We found that DEN inhibited extracellular matrix (ECM) degradation and promoted ECM synthesis. Meanwhile, DEN inhibited senescence-associated secretory phenotype (SASP) factors expression and senescence phenotype in IL-1β-treated chondrocytes. Furthermore, DEN improved mitochondrial function and reduced the production of intracellular reactive oxygen species (ROS). Also, DEN suppressed IL-1β-induced activation of the NF-κB pathway. Further, using NAC (ROS inhibitor), we found that DEN might inhibit NF-κB cascades by reducing ROS. Additionally, X-ray, micro-CT, and histological analyses in vivo demonstrated that DEN significantly alleviated cartilage inflammation, ECM degradation, and subchondral alterations in OA progression. In conclusion, DEN inhibits SASP factors expression and senescence phenotype in chondrocytes and alleviated the progression of OA via the ROS/NF-κB axis, which provides innovative strategies for the treatment of OA.

Dendrobine regulates STAT3 to attenuate mitochondrial dysfunction and senescence in vascular endothelial cells triggered by oxidized low‐density lipoprotein

“…Dendrobine has been found to inhibit the expression of senescencerelated secreted phenotypic factors and the senescence phenotype in IL-1β-treated chondrocytes, suggesting its potential efficacy in resisting cellular senescence in osteoarthritis (Chen et al, 2023).…”

“…Additionally, dendrobine exhibits promise in preventing Parkinson's disease by inhibiting dopaminergic neuronal apoptosis and suppressing endoplasmic reticulum stress through midbrain astrocyte‐derived neurotrophic factor mediation (Li, Li, et al, 2022). Dendrobine has been found to inhibit the expression of senescence‐related secreted phenotypic factors and the senescence phenotype in IL‐1β‐treated chondrocytes, suggesting its potential efficacy in resisting cellular senescence in osteoarthritis (Chen et al, 2023). These findings collectively support our discovery that dendrobine is effective in resisting EC senescence.…”

“…This study extends this understanding by demonstrating that dendrobine effectively counters the senescence process induced by ox‐LDL. Previous studies have indicated that dendrobine resists aging, prolongs lifespan, and attenuates oxidative damage and inflammation across diverse models (Chen et al, 2023; Feng et al, 2021). In specific contexts, dendrobine has been shown to resist oxidative damage in skin cells, exerting its antioxidant function through the upregulation of antioxidant enzymes and activation of the Nrf2/Keap1 signaling pathway (Yue et al, 2022).…”

Atractylenolide‐III alleviates osteoarthritis and chondrocyte senescence by targeting NF‐κB signaling

“…Furthermore, the levels of MMP13, Collagen II, and ROS, along with the ratio of healthy to collapsed mitochondrial membrane potential, were also examined. Mitochondrial dysfunction is a hallmark of cellular senescence and leads to oxidative stress through ROS elevation which, in turn, accelerates cellular senescence (Chen et al, 2023; D'Amico et al, 2022; Loeser et al, 2016; Lotz & Loeser, 2012). In addition, senescent cells produce various pro‐inflammatory proteins termed SASPs, which promote persistent inflammation and further accelerate senescence.…”

Exploring the emerging bidirectional association between inflamm‐aging and cellular senescence in organismal aging and disease

“…121 The alkaloid dendrobine suppresses cellular senescence and SASP in chondrocytes which alleviates the progression of inflammation and osteoarthritis in rats. 122 A senolytic combination of dasatinib and quercetin has been reported to suppress inflamm-aging by augmenting anti-inflammatory responses in immune functions and preventing the accumulation of senescent cells in a preclinical trial. 123 Treatment with quercetin ameliorates advanced glycation end-products-induced premature senescence and SASP in human gingival fibroblasts and has been implicated in the amelioration of inflamm-aging in diabetic periodontitis.…”