Journal
DIFFERENTIATION
Volume 89, Issue 5, Pages 128-136Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.diff.2015.06.001
Keywords
Activator of G-protein signaling 3 (AGS3); Tumor necrosis factor alpha (TNE-alpha); Dental pulp stem cells (DPSCs); Cyclic 3',5'-adenosine monophosphate (cAMP); Protein kinase A (PKA); CAMP response element (CRE)-binding protein (CREB); Osteogenic differentiation
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Funding
- Graduate Student Innovation of Science and Technology Project in Jiangsu Province [SJLX0588]
- Graduate Student Innovation of Science and Technology Project in Nantong University [YKS14015]
- Top Six Types of Talents Financial Assistance of Jiangsu Province Grant [10]
- Jiangsu Provincial Natural Science Foundation [BK2011385]
- Nantong City Social Development Projects funds [HS2012032]
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Dental pulp stem cells (DPSCs) are multipotent adult stem cells capable of differentiating along the osteoblast, adipocyte, and chondrocyte lineages. Regulating differentiation of DPSCs may be a useful tool for regenerative medicine and cell-based therapy in oral diseases. Multisignaling pathways are involved in osteogenic differentiation of DPSCs. Recent studies show that cAMP/PKA/CREB signaling could stimulate the expression of genes such as bone morphogenic proteins 2 (BMP2), inhibitor of DNA binding 2 (ID2), bone sialoprotein, osteocalcin, and type XXIV collagen, which have been implicated in osteogenesis and bone formation. Activator of G-protein signaling 3 (AGS3, gene name G-protein signaling modulator-1, Gpsml), an accessory protein for G-protein signaling, plays an important role in regulating the phosphorylation acyclic AMP response element-binding protein (p-CREB). However, the involvement of AGS3 in osteogenic differentiation of DPSCs has not been explored. Our data indicated that increased expression of AGS3 would inhibit osteogenic differentiation of DPSCs exposed to inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) via cAMP/PKA/CREB signaling. The negative role of AGS3 in osteogenic differentiation was further confirmed by knocking down and over expression of AGS3. Our findings may provide clinical implications for osteoporosis. (C) 2015 international Society of Differentiation. Published by Elsevier B.V. All rights reserved.
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