cAMP/PKA regulates osteogenesis, adipogenesis and ratio of RANKL/OPG mRNA expression in mesenchymal stem cells by suppressing leptin

Der Chih Yang, Huey Jen Tsay, Shan Yang Lin, Shih Hwa Chiou, Mei Jane Li, Tai Jay Chang, Shih Chieh Hung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

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 PPARγ2 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-κB 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.

Original languageEnglish
Article numbere1540
JournalPLoS ONE
Volume3
Issue number2
DOIs
StatePublished - 6 Feb 2008

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