Journal
PLOS ONE
Volume 3, Issue 2, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0001540
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Funding
- National Scientific Council [NSC-95-2314-B-075-047-MY3, NSC-95-2627-B-010-009-, NSC-96-2627-B-010-009-]
- National Yang-Ming University
- Ministry of Education
- Aim for the Top University Plan
- Veterans General Hospital-Taipei [V95E1-002, V95E1-003]
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Background: Mesenchymal stem cells (MSCs) are a pluripotent cell type that can differentiate into adipocytes, osteoblasts and other cells. The reciprocal relationship between adipogenesis and osteogenesis was previously demonstrated; however, the mechanisms remain largely unknown. Methods and Findings: We report that activation of PKA by 3-isobutyl-1 methyl xanthine ( IBMX) and forskolin enhances adipogenesis, the gene expression of PPAR gamma 2 and LPL, and downregulates the gene expression of Runx2 and osteopontin, markers of osteogenesis. PKA activation also decreases the ratio of Receptor Activator of the NF-kappa B Ligand to Osteoprotegerin (RANKL/OPG) gene expression-the key factors of osteoclastogenesis. All these effects are mediated by the cAMP/PKA/CREB pathway by suppressing leptin, and may contribute to PKA stimulators-induced in vivo bone loss in developing zebrafish. Conclusions: Using MSCs, the center of a newly proposed bone metabolic unit, we identified cAMP/PKA signaling, one of the many signaling pathways that regulate bone homeostasis via controlling cyto-differentiation of MSCs and altering RANKL/OPG gene expression.
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