Role of TGF-beta family in osteoclastogenesis induced by RANKL.
Recent studies have revealed that both transforming growth factor-beta (TGF-beta) and activin A play pivotal roles in osteoclastogenesis. In this report, we show that the effect of TGF-beta family members, TGF-beta1 and activin A, but not BMP-2, enhance multinucleated osteoclast-like cell (OCL) formation induced by receptor activator of NF-kappaB ligand (RANKL) in isolated bone marrow macrophages and monocytic cell line, RAW264.7. TGF-beta1 and activin A caused the growth suppression and concomitant expression of tartrate-resistant acid phosphatase (TRAP) and c-Src, without inducing syncytium formation or increasing the survival rate in RAW264.7 cells. Although TGF-beta1 and activin A had no effect on NF-kappaB and JNK activities, these factors enhanced the expression of JunB, a component of the AP-1 transcriptional complex. These results suggest that TGF-beta1 and activin A may function as commitment factors in osteoclastic differentiation, not as a crucial component for terminal differentiation to form multinucleated OCLs nor in OCL survival.
Koseki
Takeyoshi
T
Department of Oral Science, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Gao
Ying
Y
Okahashi
Nobuo
N
Murase
Yoshiyuki
Y
Tsujisawa
Toshiyuki
T
Sato
Tsuyoshi
T
Yamato
Kenji
K
Nishihara
Tatsuji
T
D000135:Acid Phosphatase / Q000378:metabolism; D028341:Activins / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D028322:Inhibin-beta Subunits / Q000494:pharmacology / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000502:physiology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000071681:Tartrate-Resistant Acid Phosphatase; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*; D053773:Transforming Growth Factor beta1
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C508961:Tgfb1 protein, mouse; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits; D016392:Proto-Oncogene Proteins pp60(c-src); D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase