BMP-2 regulation of PTHrP and osteoclastogenic factors during osteoblast differentiation of C2C12 cells.
Bone morphogenetic protein-2 (BMP-2) is strongly involved in the induction of osteoblast differentiation from mesenchymal cell precursors, as well as in enhancing bone matrix production by osteoblastic cells. Likewise, the osteoporotic phenotype of PTHrP deficient mice makes clear the importance of this paracrine regulator in bone physiology. Here, we report that BMP-2 rapidly down-regulated PTHrP gene expression through a transcriptional mechanism in pluripotent mesenchymal C2C12 cells, whereas BMP-2 increased expression of PTHrP receptor. PTHrP did not significantly alter the BMP-dependent Smad transcriptional pathway. Similarly, PTHrP did not significantly modify the BMP-regulated expression of RANKL or OPG, cytokines involved in osteoclastogenesis. More importantly, addition of PTHrP, through the PKA signaling pathway, partially prevented the BMP-dependent induction of some osteogenic markers such as Runx2 and Osterix in C2C12 cells. Our data suggest that BMP-2 down-regulation of PTHrP could facilitate terminal differentiation of osteoblasts.
Susperregui
Antonio R G
AR
IDIBELL, Departament de Ciències Fisiològiques II, Universitat de Barcelona, L'Hospitalet de Llobregat, Spain.
Viñals
Francesc
F
Ho
Patricia W M
PW
Gillespie
Matthew T
MT
Martin
T John
TJ
Ventura
Francesc
F
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D053244:Osteoprotegerin; D044162:Parathyroid Hormone-Related Protein; D053245:RANK Ligand; D044168:Receptor, Parathyroid Hormone, Type 1; D051785:Smad Proteins; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D016212:Transforming Growth Factor beta; D048308:Mitogen-Activated Protein Kinase 14