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

Alper M., Kockar F.

MOLECULAR AND CELLULAR BIOCHEMISTRY, cilt.393, sa.1-2, ss.165-175, 2014 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 393 Sayı: 1-2
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1007/s11010-014-2056-9
  • Dergi Adı: MOLECULAR AND CELLULAR BIOCHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.165-175
  • Anahtar Kelimeler: ADAM, ADAMTS, Interleukin, Osteoblasts, Jun N terminal kinase (JNK), Extracellular matrix proteins, GENE-EXPRESSION, BONE-RESORPTION, INTERLEUKIN-6, PROMOTER, BETA, BINDING, FAMILY, DIFFERENTIATION, ACTIVATION, MECHANISMS
  • Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

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.