Differential regulation of osteoadherin (OSAD) by TGF-beta1 and BMP-2.
Osteoadherin (OSAD) is a member of the small leucine rich-repeat proteoglycan (SLRP) family. SLRPs are normally found in extracellular matrices, but OSAD is the only member restricted to mineralized tissues. We investigated the promoter region of OSAD by in silico analysis and found that the proximal promoter region contains sites for Smad-3, Smad-4, and AP-1. All are effectors of TGF-beta family signalling. We tested sensitivity of the promoter to the two TGF-beta family members TGF-beta1 and BMP-2. We found TGF-beta1 to down regulate OSAD, while BMP-2 up regulates OSAD. As a consequence of how OSAD is regulated by TGF-beta1 and BMP-2 and its temporal expression pattern in osteoblasts and bone development, we can conclude OSAD as an early marker for terminally differentiated matrix producing osteoblasts.
Rehn
Anders P
AP
Center for Oral Biology, Karolinska Institutet, Box 4064, 141 04 Huddinge, Sweden. anders.rehn@ki.se <anders.rehn@ki.se>
Chalk
Alistair M
AM
Wendel
Mikael
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D019295:Computational Biology; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C113360:osteoadherin