Document Detail

Enhanced mitochondrial biogenesis contributes to Wnt induced osteoblastic differentiation of C3H10T1/2 cells.
MedLine Citation:
PMID:  20399290     Owner:  NLM     Status:  MEDLINE    
Mitochondria play a key role in cell physiology including cell differentiation and proliferation. We investigated the changes of mitochondrial biogenesis during Wnt-induced osteoblastic differentiation of murine mesenchymal C3H10T1/2 cells. Scanning electron microscopy demonstrated that activation of Wnt signaling by Wnt-3A conditioned medicum (CM) resulted in significant increase in the number of mitochondria in C3H10T1/2 cells. In addition, the induction of alkaline phosphatase (ALP) activities by Wnt-3A CM was accompanied by significant increase in mitochondrial mass (p<0.05), mitochondrial membrane potential (p<0.05), intracellular reactive oxygen species production (p<0.05), resting oxygen consumption rate (p<0.05), cellular ATP content (p< or =0.05) and mtDNA copy number (p<0.05) compared to the cells with control CM (L292-CM) treatment. Moreover, co-treatment with Dkk-1 or WIF-1, both of which are Wnt inhibitors, abrogated the Wnt-3A-induced ALP activities as well as mitochondrial biogenesis markers. Upregulation of mitochondrial biogenesis by overexpression of mitochondrial transcription factor A (Tfam) significantly enhanced Wnt-induced osteogenesis as measured by ALP activities. In contrast, inhibition of mitochondrial biogenesis by treatment with Zidovudine (AZT) resulted in significant inhibition of ALP activities. Finally, ALP activities in human osteosarcoma cell line devoid of mitochondrial DNA (rho(0) cells) was significantly suppressed both in basal and Wnt-3A stimulated state compared to those from mitochondria-intact cells (rho+ cells). As a mechanism for Wnt-mediated mitochondrial biogenesis, we found that Wnt increased the expression of PGC-1alpha, a critical molecules in mitochondrial biogenesis, through Erk and p38 MAPK pathway independent of beta-catenin signaling. We also found that increased mitochondrial biogenesis is in turn positively regulating TOPflash reporter activity as well as beta-catenin levels. To summarize, mitochodrial biogenesis is upregulated by Wnt signaling and this upregulation contributes to the osteoblastic differentiation of mouse mesenchymal C3H10T1/2 cells.
Jee Hyun An; Jae-Yeon Yang; Byung Yong Ahn; Sun Wook Cho; Ju Yeon Jung; Hwa Young Cho; Young Min Cho; Sang Wan Kim; Kyong Soo Park; Seong Yeon Kim; Hong Kyu Lee; Chan Soo Shin
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-14
Journal Detail:
Title:  Bone     Volume:  47     ISSN:  1873-2763     ISO Abbreviation:  Bone     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-23     Completed Date:  2010-09-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8504048     Medline TA:  Bone     Country:  United States    
Other Details:
Languages:  eng     Pagination:  140-50     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Inc. All rights reserved.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
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MeSH Terms
Adipogenesis / drug effects
Cell Differentiation / drug effects*
Cell Line
Culture Media, Conditioned / pharmacology
Gene Expression Regulation / drug effects
Mitochondria / drug effects*,  metabolism*
Mitogen-Activated Protein Kinases / metabolism
Osteoblasts / cytology*,  drug effects*,  enzymology,  ultrastructure
Osteogenesis / drug effects
Trans-Activators / genetics,  metabolism
Transcription, Genetic / drug effects
Wnt Proteins / pharmacology*
beta Catenin / genetics,  metabolism
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Ppargc1a protein, mouse; 0/Trans-Activators; 0/Wnt Proteins; 0/Wnt-3 protein; 0/beta Catenin; EC Protein Kinases

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