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


RESULTS
We report that activation of PKA by 3-isobutyl-1 methyl xanthine (IBMX) and forskolin enhances adipogenesis, the gene expression of PPARgamma2 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-kappaB 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.
Yang
Der-Chih
DC
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Tsay
Huey-Jen
HJ
Lin
Shan-Yang
SY
Chiou
Shih-Hwa
SH
Li
Mei-Jane
MJ
Chang
Tai-Jay
TJ
Hung
Shih-Chieh
SC
D050156:Adipogenesis; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D005260:Female; D006801:Humans; D020738:Leptin / Q000037:antagonists & inhibitors*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D010012:Osteogenesis; D053244:Osteoprotegerin / Q000032:analysis / Q000235:genetics*; D053245:RANK Ligand / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D015027:Zebrafish
D020738:Leptin; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D017868:Cyclic AMP-Dependent Protein Kinases