IL-6 upregulates a disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAMTS-2) in human osteosarcoma cells mediated by JNK pathway

Mol Cell Biochem. 2014 Aug;393(1-2):165-75. doi: 10.1007/s11010-014-2056-9. Epub 2014 Apr 22.

Abstract

ADAMTS-2 and ADAMTS-3 (a disintegrin and metalloproteinase with thrombospondin type 1 motif 2) belong to the procollagen aminoproteinase subfamily of ADAMTS proteases. They play crucial roles in the collagen metabolism. To understand the regulation of ADAMTS-2 gene expression in osteoblastic cells, we have cloned a functional 760 bp of human ADAMTS-2 promoter. Sequence analysis of the ADAMTS-2 promoter region showed the absence of a TATA box, but identified a GC box, a CpG island, several GAGA boxes and several transcriptional factor binding sites, which may be valuable in the regulation of ADAMTS-2 transcription. We also elucidated that Interleukin 6 (IL-6) increases ADAMTS-2 and ADAMTS-3 mRNA and protein levels in different osteosarcoma cell lines namely, MG-63 and Saos-2. IL-6 also increases the transcriptional activation of the ADAMTS-2 gene promoter. Pathway inhibition studies revealed that ADAMTS-2 upregulation by IL-6 was mediated by JNK pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / biosynthesis*
  • ADAM Proteins / genetics
  • ADAMTS Proteins
  • ADAMTS4 Protein
  • Cell Line, Tumor
  • Extracellular Matrix Proteins / biosynthesis
  • Humans
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism
  • MAP Kinase Signaling System
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • Procollagen N-Endopeptidase / biosynthesis*
  • Procollagen N-Endopeptidase / genetics
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • Transcriptional Activation / genetics*

Substances

  • Extracellular Matrix Proteins
  • Interleukin-6
  • RNA, Messenger
  • ADAM Proteins
  • ADAMTS Proteins
  • ADAMTS3 protein, human
  • ADAMTS2 protein, human
  • Procollagen N-Endopeptidase
  • ADAMTS4 Protein