12531559

pubmed:Citation

6

In this study, we examine the role of bone morphogenetic protein (BMP) signaling during differentiation of the murine preosteoblastic KS483 cell line, which formed alkaline phosphatase (ALP)-positive and mineralized nodules during a 3 week culture period. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) demonstrated the presence of various BMPs (BMP-2, -3, -4, -6, -7, and -8A and -8B), BMP type I and II receptors (ALK2, ALK3, ALK4, BMPR-II, and ActR-IIA and -IIB), BMP antagonists (DAN, gremlin, chordin, cerberus, noggin, and tsg), and Smads 1-8. mRNA expression of these genes did not change during differentiation, except for BMP-3, BMP-8a, and noggin. BMP-3 increased gradually, particularly in the matrix formation phase; BMP-8a was induced from the onset of matrix maturation and mineralization, in parallel to the expression of osteocalcin; and noggin tended to decline during the mineralization phase. Treatment of KS483 cells with the BMP antagonists noggin or soluble truncated BMPR-IA, either continuously or during distinct periods of osteoblast differentiation; that is, matrix formation or matrix maturation and mineralization phase, decreased ALP-positive and mineralized nodule area independent of the phase of osteoblast differentiation. Notably, the antagonists inhibited mineralization of already existing nodules. Similarly, BMP-4 stimulated differentiation not only at the beginning of the culture period, but also at late stages of differentiation. These data indicate that autocrine BMP signaling is involved in KS483 osteoblastic differentiation not only during the early phase of differentiation, but also during matrix maturation and mineralization. The different expression patterns of components of BMP signaling in the KS483 cells suggest distinct functions of individual BMPs during osteoblast differentiation. In summary, our data suggest that BMP activity is required not only for initiation of osteoblast differentiation and further development of early osteoblasts, but is also involved in late-stage osteoblast differentiation and matrix mineralization.

http://linkedlifedata.com/resource/pubmed/journal/8504048

http://linkedlifedata.com/resource/pubmed/chemical/Activin Receptors, Type I, http://linkedlifedata.com/resource/pubmed/chemical/BMPR1A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/BMPR2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Bmpr1a protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Bmpr2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein..., http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein..., http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cktsf1b1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/GREM1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Xenopus Proteins, http://linkedlifedata.com/resource/pubmed/chemical/cerberus protein, Xenopus, http://linkedlifedata.com/resource/pubmed/chemical/chordin

Dec

pubmed-author:DeckersM M LMM, pubmed-author:HoogendamJJ, pubmed-author:KarperienMM, pubmed-author:LöwikC W G MCW, pubmed-author:VisserAA, pubmed-author:van BezooijenR LRL, pubmed-author:van der HorstGG

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NLM

661-9

pubmed-meshheading:12531559-Activin Receptors, Type I, pubmed-meshheading:12531559-Animals, pubmed-meshheading:12531559-Autocrine Communication, pubmed-meshheading:12531559-Bone Morphogenetic Protein Receptors, Type I, pubmed-meshheading:12531559-Bone Morphogenetic Protein Receptors, Type II, pubmed-meshheading:12531559-Bone Morphogenetic Proteins, pubmed-meshheading:12531559-Cell Differentiation, pubmed-meshheading:12531559-Cell Line, pubmed-meshheading:12531559-Glycoproteins, pubmed-meshheading:12531559-Humans, pubmed-meshheading:12531559-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:12531559-Mice, pubmed-meshheading:12531559-Osteoblasts, pubmed-meshheading:12531559-Protein-Serine-Threonine Kinases, pubmed-meshheading:12531559-Proteins, pubmed-meshheading:12531559-Receptors, Growth Factor, pubmed-meshheading:12531559-Signal Transduction, pubmed-meshheading:12531559-Stem Cells, pubmed-meshheading:12531559-Xenopus Proteins

Differentiation of murine preosteoblastic KS483 cells depends on autocrine bone morphogenetic protein signaling during all phases of osteoblast formation.

Journal Article