Janus kinase 2/signal transducer and activator of transcription 3 path-ways mediate effect of leptin on expression of catabolic genes in rat nu-cleus pulposus cells / 中国病理生理杂志

ABSTRACT

AIM:To explore the effect of leptin on the expression of degeneration-related genes in rat nucleus pulposus ( NP) cells and to detect the possible mechanism .METHODS:The normal NP cells isolated from SD rats were analyzed by immunochemistry and immunofluorescence for the collagen II and cytokeratin 19 expression.The NP cells were treated with leptin and/or interleukin-1β( IL-β).The mRNA expression of MMP-1, MMP-3, MMP-9, MMP-13, ADAMTS-4, ADAMTS-5, aggrecan and COL2A1 in the cells was detected by real-time PCR.Alcian blue staining and im-munochemistry were used to examine the expression of proteoglycan and collagen II .Activation of involved pathways was studied by Western blot .The inhibitors of the pathways were used to reveal the effect of these pathways on NP cells .RE-SULTSThe results of real-time PCR revealed that leptin alone up-regulated the mRNA expression of MMP-1, MMP-13, ADAMTS-4, ADAMTS-5 and COL2A1.The synergy of leptin and IL-βwas found in the increased expression of MMP-1, MMP-3 and ADAMTS-5.The NP cells treated with leptin showed less expression of collagen II .Both PI3K/Akt and JAK2/SATA3 pathways were activated by leptin , whereas only inhibitor of JAK 2/SATA3 pathway reversed the expression of MMP-1 and MMP-13.CONCLUSION:Leptin may promote catabolism in rat NP cells via JAK2/SATA3 pathways, which may be the mechanism mediating the association between obesity and intervertebral disc degeneration .