Leptin Downregulates Aggrecan through the p38-ADAMST Pathway in Human Nucleus Pulposus CellsReportar como inadecuado




Leptin Downregulates Aggrecan through the p38-ADAMST Pathway in Human Nucleus Pulposus Cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

The mechanistic basis of obesity-associated intervertebral disc degeneration IDD is unclear. Aberrant expression of aggrecan and its degrading enzymes ADAMTS-4 and ADAMTS-5 is implicated in the development of IDD. Here, we investigated the effect of leptin, a hormone with increased circulating levels in obesity, on the expression of aggrecan and ADAMTSs in primary human nucleus pulposus NP cells. Real-time PCR and Western blots showed that leptin increased the mRNA and protein expression of ADAMTS-4 and ADAMTS-5 and reduced the level of aggrecan in NP cells, accompanied by a prominent induction of p38 phosphorylation. Treatment of NP cells with SB203580 a p38 inhibitor abolished the regulation of aggrecan and ADAMTSs by leptin. Knockdown of ADAMTS-4 and ADAMTS-5 by siRNAs also attenuated the degradation of aggrecan in leptin-stimulated NP cells. To conclude, we demonstrated that leptin induces p38 to upregulate ADAMTSs and thereby promoting aggrecan degradation in human NP cells. These results provide a novel mechanistic insight into the molecular pathogenesis of obesity-associated IDD.



Autor: Zheng Li , Xin Yu , Jinqian Liang, William Ka Kei Wu, Jun Yu, Jianxiong Shen

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados