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Open AccessArticle

Effect of cAMP Signaling Regulation in Osteogenic Differentiation of Adipose-Derived Mesenchymal Stem Cells

Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, 02-004 Warsaw, Poland
Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warsaw, Poland
Laboratory for Cell Research and Application, Medical University of Warsaw, 02-097 Warsaw, Poland
Authors to whom correspondence should be addressed.
Cells 2020, 9(7), 1587;
Received: 30 January 2020 / Revised: 25 June 2020 / Accepted: 26 June 2020 / Published: 30 June 2020
(This article belongs to the Special Issue New Advances in Cyclic AMP Signalling)
The successful implementation of adipose-derived mesenchymal stem cells (ADSCs) in bone regeneration depends on efficient osteogenic differentiation. However, a literature survey and our own experience demonstrated that current differentiation methods are not effective enough. Since the differentiation of mesenchymal stem cells (MSCs) into osteoblasts and adipocytes can be regulated by cyclic adenosine monophosphate (cAMP) signaling, we investigated the effects of cAMP activator, forskolin, and inhibitor, SQ 22,536, on the early and late osteogenic differentiation of ADSCs cultured in spheroids or in a monolayer. Intracellular cAMP concentration, protein kinase A (PKA) activity, and inhibitor of DNA binding 2 (ID2) expression examination confirmed cAMP up- and downregulation. cAMP upregulation inhibited the cell cycle and protected ADSCs from osteogenic medium (OM)-induced apoptosis. Surprisingly, the upregulation of cAMP level at the early stages of osteogenic differentiation downregulated the expression of osteogenic markers RUNX2, Osterix, and IBSP, which was more significant in spheroids, and it is used for the more efficient commitment of ADSCs into preosteoblasts, according to the previously reported protocol. However, cAMP upregulation in a culture of ADSCs in spheroids resulted in significantly increased osteocalcin production and mineralization. Thus, undifferentiated and predifferentiated ADSCs respond differently to cAMP pathway stimulation in terms of osteogenesis, which might explain the ambiguous results from the literature. View Full-Text
Keywords: osteogenic differentiation; cAMP; mesenchymal stem cells osteogenic differentiation; cAMP; mesenchymal stem cells
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Rumiński, S.; Kalaszczyńska, I.; Lewandowska-Szumieł, M. Effect of cAMP Signaling Regulation in Osteogenic Differentiation of Adipose-Derived Mesenchymal Stem Cells. Cells 2020, 9, 1587.

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