Cyclic AMP signaling in bone marrow stromal cells has reciprocal effects on the ability of mesenchymal stem cells to differentiate into mature osteoblasts versus mature adipocytes.
Stimulatory G protein-mediated cAMP signaling is intimately involved in skeletal homeostasis. However, limited information is available on the role of the cAMP signaling in regulating the differentiation of mesenchymal stem cells into mature osteoblasts and adipocytes. To investigate this, we treated primary mouse bone marrow stromal cells (BMSCs) with forskolin to stimulate cAMP signaling and determined the effect on osteoblast and adipocyte differentiation. Exposure of differentiating osteoblasts to forskolin markedly inhibited progression to the late stages of osteoblast differentiation, and this effect was replicated by continuous exposure to PTH. Strikingly, forskolin activation of cAMP signaling in BMSCs conditioned mesenchymal stem cells (MSCs) to undergo increased osteogenic differentiation and decreased adipogenic differentiation. PTH treatment of BMSCs also enhanced subsequent osteogenesis, but promoted an increased adipogenesis as well. Thus, activation of cAMP signaling alters the lineage commitment of MSCs, favoring osteogenesis at the expense of adipogenesis.
University of California, San Francisco, San Francisco, CA, USA.
Richard
R
Kao
Weidar
W
Lu
Alyssa
A
Louie
Robert
R
Nissenson
D017667:Adipocytes / Q000502:physiology*; D050156:Adipogenesis / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D010006:Osteoblasts / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology*; D060509:Wnt3A Protein / Q000494:pharmacology
D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D060509:Wnt3A Protein; D005576:Colforsin; D012313:RNA; D000242:Cyclic AMP; D000469:Alkaline Phosphatase