Induction of human ADAMTS-2 gene expression by IL-1α is mediated by a multiple crosstalk of MEK/JNK and PI3K pathways in osteoblast like cells

The present study, for the first time, demonstrated that IL-1α increases ADAMTS-2 and ADAMTS-3 gene expressions in both Saos-2 and MG-63 cells. Having correlation to mRNA induction, the upregulation of ADAMTS-2,-3 protein levels by IL-1α stimulation is also observed. The inhibition studies showed that this upregulation occurred at the level of transcription, and there was no effect of IL-1α on ADAMTS-2 mRNA half-life in Saos-2 cells. Transactivation potential of IL-1α on ADAMTS-2 promoter was investigated by transient transfection assay. Specifically, IL-1α strongly increased − 658/+ 112 and − 530/+ 112 ADAMTS-2 promoter constructs. Further, we analyzed signaling pathways involved in ADAMTS-2 induction. Pathway inhibition studies revealed that this upregulation depends on the activation of MEK, JNK and PI3K pathways. These findings suggested that IL-1α is a strong positive regulator of ADAMTS-2 and ADAMTS-3 expression. These findings would provide novel insight into the pathophysiology of OA.