Leptin modulates the expression of catabolic genes in rat nucleus pulposus cells through the mitogenactivated protein kinase and Janus kinase 2/signal transducer and activator of transcription 3 pathways
Obesity has been demonstrated to be involved in the progress of intervertebral disc degeneration (IDD). However, the associated mechanisms remain to be elucidated. The purpose the present study was to examine the effect of leptin on the expression of degenerationassociated genes in rat nucleus pulposus (NP) cells, and determine the possible mechanism. Normal NP cells, obtained from Sprague Dawley rats, were identified using immunocytochemistry for the expression of collagen II and CA125, and treated with leptin and/or interleukin (IL)β. Subsequently, the mRNA expression levels of matrix metalloproteinase (MMP)1, MMP3, MMP9, MMP13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, ADAMTS5, aggrecan and COL2A1 were detected by reverse transcriptionquantitative polymerase chain reaction (RT-qPCR). Alcian staining and immunocytochemistry were used to examine the expression levels of proteoglycan and collagen II. The pathway activation was investigated using western blotting, and inhibitors of the pathways were used to reveal the effect of these pathways on the NP cells. The results of the RT-qPCR demonstrated that leptin alone upregulated the mRNA expression levels of MMP1, MMP13, ADAMTS4, ADAMTS5 and COL2A1. Synergy of leptin and ILβ was found in the increased expression levels of MMP1, MMP3 and ADAMTS5. The leptin-treated NP cells exhibited decreased expression of collagen II. The mitrogen-activated protein kinase (MAPK) pathway (c-Jun-N-terminal kinase, phosphorylated extracellular signal-regulated kinase and p38), phosphatidylinositol 3-kinase (PI3K)/Akt pathway and Janus kinase (JAK)2/signal transducer and activator of transcription 3 pathway were all activated by leptin, however, inhibitors of all the pathways, with the exception of the PI3K/Akt pathway, reversed the expression levels of MMP1 and MMP13. These results suggested that leptin promoted catabolic metabolism in the rat NP cells via the MAPK and JAK2/STAT3 pathways, which may be the mechanism mediating the association between obesity and IDD.
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Document Type: Research Article
Affiliations: Department of Orthopedic Surgery, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang 325200, P.R. China
Publication date: August 1, 2015
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