Document Detail

Activation of caspases is required for osteoblastic differentiation.
MedLine Citation:
PMID:  12954609     Owner:  NLM     Status:  MEDLINE    
Previous studies have shown that mouse osteoblastic MC3T3-E1 cells undergo apoptosis when exposed to a mixture of proinflammatory cytokines. Bone morphogenetic protein (BMP)s are important regulators of osteoblast differentiation. Because regulation of osteoblastic differentiation is poorly understood, we sought to determine if BMP-4-induced differentiation of osteoblastic cells depends on the activity of the key apoptotic proteases, i.e. the caspases. BMP-4 induced the growth arrest and differentiation of osteoblastic cell line MC3T3-E1, as evidenced by the appearance of osteoblastic phenotypes such as alkaline phosphatase (ALP) activation and parathyroid hormone (PTH)-dependent production of cAMP. Surprisingly, BMP-4 induced transient and potent activation of caspase-8, caspase-2, and caspase-3, in this order. However, no apoptosis or necrosis in BMP-4-treated cells could be detected by FACS using annexin-V/propodium iodine double staining. Peptide inhibition of caspase activity led to a dramatic reduction in ALP activation and PTH-induced production of cAMP in BMP-4-treated cells. Although BMP-4 treatment resulted in cell-cycle G0/G1 arrest as detected by FACS cell-cycle analysis, caspase inhibitors (caspase-8, caspase-2, and caspase-3 inhibitors) could block the G0/G1 arrest in MC3T3-E1 cells. Taken together, these results confirm a unique and unanticipated role for the caspase-mediated signal cascade in the differentiation of osteoblasts.
Makio Mogi; Akifumi Togari
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-09-03
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-11-24     Completed Date:  2004-01-12     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  47477-82     Citation Subset:  IM    
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya 464-8650, Japan.
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MeSH Terms
Alkaline Phosphatase / metabolism
Blotting, Western
Bone Morphogenetic Protein 4
Bone Morphogenetic Proteins / metabolism
Caspase 2
Caspase 3
Caspase 8
Caspase 9
Caspases / metabolism*
Cell Cycle
Cell Differentiation
Cell Division
Cell Line
Cell Separation
Cyclic AMP / metabolism
Enzyme Activation
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Osteoblasts / cytology*
Parathyroid Hormone / metabolism
Time Factors
Reg. No./Substance:
0/Bmp4 protein, mouse; 0/Bone Morphogenetic Protein 4; 0/Bone Morphogenetic Proteins; 0/Parathyroid Hormone; 60-92-4/Cyclic AMP; EC Phosphatase; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Casp8 protein, mouse; EC 3.4.22.-/Casp9 protein, mouse; EC 3.4.22.-/Caspase 2; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 8; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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