Changes in bone morphogenetic protein receptor-IB localisation regulate osteogenic responses of human bone cells to bone morphogenetic protein-2.
Cell responses to bone morphogenetic proteins (BMP) depend on the expression and surface localisation of transmembrane receptors BMPR-IA, -IB and -II. The present study shows that all three antigens are readily detected in human bone cells. However, only BMPR-II was found primarily at the plasma membrane, whereas BMPR-IA was expressed equally in the cytoplasm and at the cell surface. Notably, BMPR-IB was mainly intracellular, where it was associated with a number of cytoplasmic structures and possibly the nucleus. Treatment with transforming growth factor beta1 (TGF-beta1) caused rapid translocation of BMPR-IB to the cell surface, mediated via the p38 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways. The TGF-beta1-induced increase in surface BMPR-IB resulted in significantly elevated BMP-2 binding and Smad1/5/8 phosphorylation, although the receptor was subsequently internalised and the functional response to BMP-2 consequently down-regulated. The results show, for the first time, that BMPR-IB is localised primarily in intracellular compartments in bone cells and that TGF-beta1 induces rapid surface translocation from the cytoplasm to the cell surface, resulting in increased sensitivity of the cells to BMP-2.
Singhatanadgit
Weerachai
W
Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, United Kingdom.
Mordan
Nicky
N
Salih
Vehid
V
Olsen
Irwin
I
D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism* / Q000494:pharmacology; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D001842:Bone and Bones / Q000166:cytology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010011:Osteocytes / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology
D055396:Bone Morphogenetic Protein 2; D053773:Transforming Growth Factor beta1; D052005:Bone Morphogenetic Protein Receptors, Type I