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PMID: 12379805 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Bone morphogenetic protein and retinoic acid signaling cooperate to induce osteoblast differentiation of preadipocytes.

The Journal of cell biology ·Vol. 159 ·No. 1 ·2002-10-14 ·Pages 135-46

Skillington J, Choy L, Derynck R

Abstract

Mesenchymal cells can differentiate into osteoblasts, adipocytes, myoblasts, or chondroblasts. Whether mesenchymal cells that have initiated differentiation along one lineage can transdifferentiate into another is largely unknown. Using 3T3-F442A preadipocytes, we explored whether extracellular signals could redirect their differentiation from adipocyte into osteoblast. 3T3-F442A cells expressed receptors and Smads required for bone morphogenetic protein (BMP) signaling. BMP-2 increased proliferation and induced the early osteoblast differentiation marker alkaline phosphatase, yet only mildly affected adipogenic differentiation. Retinoic acid inhibited adipose conversion and cooperated with BMP-2 to enhance proliferation, inhibit adipogenesis, and promote early osteoblastic differentiation. Expression of BMP-RII together with BMP-RIA or BMP-RIB suppressed adipogenesis of 3T3-F442A cells and promoted full osteoblastic differentiation in response to retinoic acid. Osteoblastic differentiation was characterized by induction of cbfa1, osteocalcin, and collagen I expression, and extracellular matrix calcification. These results indicate that 3T3-F442A preadipocytes can be converted into fully differentiated osteoblasts in response to extracellular signaling cues. Furthermore, BMP and retinoic acid signaling cooperate to stimulate cell proliferation, repress adipogenesis, and promote osteoblast differentiation. Finally, BMP-RIA and BMP-RIB induced osteoblast differentiation and repressed adipocytic differentiation to a similar extent.

MeSH Terms
Adipocytes/cytology,drug effects,physiology Alkaline Phosphatase/metabolism Animals Bone Morphogenetic Protein 2 Bone Morphogenetic Protein Receptors, Type I Bone Morphogenetic Protein Receptors, Type II Bone Morphogenetic Proteins/metabolism,pharmacology Cell Differentiation/drug effects,physiology Cell Division/physiology Cell Line Cell Size Complement Factor D Drug Synergism Humans Insulin/pharmacology Mice Osteoblasts/cytology,physiology Protein Serine-Threonine Kinases/metabolism Receptors, Cytoplasmic and Nuclear/metabolism Receptors, Growth Factor/metabolism Serine Endopeptidases/metabolism Signal Transduction/physiology Transcription Factors/metabolism Transforming Growth Factor beta Tretinoin/pharmacology
Chemicals
BMP2 protein, human Bmp2 protein, mouse Bone Morphogenetic Protein 2 Bone Morphogenetic Proteins Insulin Receptors, Cytoplasmic and Nuclear Receptors, Growth Factor Transcription Factors Transforming Growth Factor beta Tretinoin Protein Serine-Threonine Kinases BMPR2 protein, human Bmpr2 protein, mouse Bone Morphogenetic Protein Receptors, Type I Bone Morphogenetic Protein Receptors, Type II Alkaline Phosphatase Serine Endopeptidases CFD protein, human Complement Factor D complement factor D, mouse
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Skillington Jeremy
Department of Growth and Development, Programs in Cell Biology and Developmental Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
Choy Lisa
Derynck Rik
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200204060
Published
2002-10-14
Epub
2002-00-14
Pages
135-46
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173483
Subset
IM
Grants
NCI NIH HHS · CA63101 · United States
NCI NIH HHS · R01 CA063101 · United States
NIDCR NIH HHS · DE-13058 · United States
NIDCR NIH HHS · P60 DE013058 · United States
NIDDK NIH HHS · K01 DK02877 · United States
External Links
PubMed source DOI: 10.1083/jcb.200204060 PMC Full Text View journal details
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