Kai Feng1, Hongfang Chen2, Chen Xu3. 1. Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. jsycfk@126.com. 2. Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. 3. Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. 116126@sh9hospital.org.
Abstract
OBJECTIVE: Osteoarthritis (OA) is a degenerative articular cartilage disease accompanied by superfluous apoptosis of chondrocytes in the elderly. Celastrol is a potent bioactive medicine which can exert anti-inflammatory and anti-oxidative effects in various diseases. This study aimed to elucidate the possible role of celastrol in OA as well as the specific mechanism of celastrol in vitro and in vivo. METHODS: Autophagy-related biomarkers and apoptotic molecules were evaluated by PCR, Western blot and immunofluorescence staining. The level of autophagy was assessed by MDC staining and transmission electron microscopy. To study the downstream signaling pathway, nuclear factor kappa B (NF-κB) signaling pathway-related proteins were examined by Western blot. Moreover, an anterior cruciate ligament transection (ACLT) rat model was established to observe the protective effect of celastrol on rat cartilage. RESULTS: We found celastrol ameliorated IL-1β-induced chondrocyte apoptosis and increased the expression of LC3-II and Beclin-1. In addition, the suppression of celastrol-induced autophagy by 3-methyladenine (3MA) prevented the protective effect of celastrol in chondrocytes. Moreover, celastrol decreased the IL-1β-stimulated phosphorylation degree of IκBα and P65. We also found PDTC (a known NF-κB pathway inhibitor) can promote the activation of autophagy and attenuate the apoptosis of chondrocytes. Meanwhile, the results of rat ACLT model revealed the same effect as in vitro experiments. CONCLUSIONS: In summary, celastrol protected against chondrocyte apoptosis by promoting autophagy and inhibiting NF-κB signaling pathway in vitro and in vivo.
OBJECTIVE:Osteoarthritis (OA) is a degenerative articular cartilage disease accompanied by superfluous apoptosis of chondrocytes in the elderly. Celastrol is a potent bioactive medicine which can exert anti-inflammatory and anti-oxidative effects in various diseases. This study aimed to elucidate the possible role of celastrol in OA as well as the specific mechanism of celastrol in vitro and in vivo. METHODS: Autophagy-related biomarkers and apoptotic molecules were evaluated by PCR, Western blot and immunofluorescence staining. The level of autophagy was assessed by MDC staining and transmission electron microscopy. To study the downstream signaling pathway, nuclear factor kappa B (NF-κB) signaling pathway-related proteins were examined by Western blot. Moreover, an anterior cruciate ligament transection (ACLT) rat model was established to observe the protective effect of celastrol on ratcartilage. RESULTS: We found celastrol ameliorated IL-1β-induced chondrocyte apoptosis and increased the expression of LC3-II and Beclin-1. In addition, the suppression of celastrol-induced autophagy by 3-methyladenine (3MA) prevented the protective effect of celastrol in chondrocytes. Moreover, celastrol decreased the IL-1β-stimulated phosphorylation degree of IκBα and P65. We also found PDTC (a known NF-κB pathway inhibitor) can promote the activation of autophagy and attenuate the apoptosis of chondrocytes. Meanwhile, the results of rat ACLT model revealed the same effect as in vitro experiments. CONCLUSIONS: In summary, celastrol protected against chondrocyte apoptosis by promoting autophagy and inhibiting NF-κB signaling pathway in vitro and in vivo.
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