Celastrol reduces IL-1ß induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo.

Chen, Jian; Xuan, Jun; Gu, Yun-Tao; Shi, Ke-Si; Xie, Jun-Jun; Chen, Jiao-Xiang; Zheng, Zeng-Ming; Chen, Yu; Chen, Xi-Bang; Wu, Yao-Sen; Zhang, Xiao-Lei; Wang, Xiang-Yang

Chen, Jian; Xuan, Jun; Gu, Yun-Tao; Shi, Ke-Si; Xie, Jun-Jun; Chen, Jiao-Xiang; Zheng, Zeng-Ming; Chen, Yu; Chen, Xi-Bang; Wu, Yao-Sen; Zhang, Xiao-Lei; Wang, Xiang-Yang.

Afiliación

Chen J; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
Xuan J; Jinhua Municipal Central Hospital, Jinhua Hospital of Zhejiang University, People's Republic of China.
Gu YT; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
Shi KS; The First Clinical College, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China.
Xie JJ; Department of Postgraduate Education, Wenzhou Medical University, Wenzhou, 325027, People's Republic of China.
Chen JX; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
Zheng ZM; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
Chen Y; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
Chen XB; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
Wu YS; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
Zhang XL; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China. Electronic address: callmeroger@126.com.
Wang XY; Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China. Electronic address: xiangyangwang2016@163.com.

Biomed Pharmacother ; 91: 208-219, 2017 Jul.

Article en En | MEDLINE | ID: mdl-28458159

RESUMEN

Celastrol has been reported to exert therapeutic potential on pro-inflammatory diseases including asthma, Crohn's disease, arthritis and neurodegenerative disorders via inhibiting NF-κB pathway. While the effect of celastrol on intervertebral disc degeneration (IDD), which is also a pro-inflammatory disease, remains unknown. In this study, we evaluated the effect of celastrol on IDD in IL-1ß treated human nucleus pulposus cells in vitro as well as in puncture induced rat IDD model in vivo. Our results showed that celastrol reduced the expression of catabolic genes (MMP-3, 9, 13, ADAMTS-4, 5), oxidative stress factors (COX-2, iNOS) and pro-inflammatory factors (IL-6, TNF-a) induced by IL-1ß in nucleus pulposus cells, also phosphorylation of IκBα and p65 were attenuated by celastrol, indicating NF-κB pathway was inhibited by celastrol in nucleus pulposus cells. In vivo study showed that celastrol treated rats had stronger T2-weighted signal than vehicle-treated rats at 2 weeks and 6 weeks' time point, suggesting celastrol could attenuate intervertebral disc degeneration in vivo. Together, our study demonstrates that celastrol could reduce IL-1ß induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo, which shows its potential to be a therapeutic drug for IDD.

Asunto(s)

Matriz Extracelular/metabolismo; Inflamación/patología; Interleucina-1beta/farmacología; Degeneración del Disco Intervertebral/patología; Núcleo Pulposo/patología; Estrés Oxidativo; Triterpenos/uso terapéutico; Proteína ADAMTS5/metabolismo; Agrecanos/genética; Agrecanos/metabolismo; Animales; Muerte Celular/efectos de los fármacos; Núcleo Celular/efectos de los fármacos; Núcleo Celular/metabolismo; Supervivencia Celular/efectos de los fármacos; Colágeno Tipo II/genética; Colágeno Tipo II/metabolismo; Ciclooxigenasa 2/metabolismo; Citoprotección/efectos de los fármacos; Regulación de la Expresión Génica/efectos de los fármacos; Humanos; Interleucina-6/metabolismo; Degeneración del Disco Intervertebral/genética; Imagen por Resonancia Magnética; Masculino; FN-kappa B/metabolismo; Óxido Nítrico Sintasa de Tipo II/metabolismo; Estrés Oxidativo/efectos de los fármacos; Triterpenos Pentacíclicos; Transporte de Proteínas/efectos de los fármacos; ARN Mensajero/genética; ARN Mensajero/metabolismo; Ratas Sprague-Dawley; Factor de Crecimiento Transformador beta/metabolismo; Triterpenos/farmacología; Factor de Necrosis Tumoral alfa/metabolismo

Palabras clave

Celastrol; Inflammation; Intervertebral disc degeneration; NF-κB

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triterpenos / Estrés Oxidativo / Matriz Extracelular / Interleucina-1beta / Degeneración del Disco Intervertebral / Núcleo Pulposo / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Biomed Pharmacother Año: 2017 Tipo del documento: Article Pais de publicación: Francia

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