title: AGS3 is involved in TNF-α medicated osteogenic differentiation of human dental pulp stem cells.
abstract: 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, Gpsm1), an accessory protein for G-protein signaling, plays an important role in regulating the phosphorylation of cyclic 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 α (TNF-α) 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.
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, China.
authors.forename: Min
authors.initials: M
authors.lastname: Lian
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, China.
authors.forename: Qijie
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, China.
authors.forename: Guijuan
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Hematology, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Liren
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Spine Surgery, the Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Jinglong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Spine Surgery, the Second Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: You
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, Nantong, China. Electronic address: zdm060808@aliyun.com.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, China. Electronic address: fengxingmei1220@163.com.
authors.forename: Xingmei
authors.initials: X
authors.lastname: Feng
mesh_terms: D000328:Adult; D000368:Aged; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology*; D005786:Gene Expression Regulation; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000502:physiology*; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism; D058574:Integrin-Binding Sialoprotein / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
chemical_list: D019485:Bone Morphogenetic Proteins; C525615:GPSM1 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D051797:Inhibitor of Differentiation Protein 2; D058574:Integrin-Binding Sialoprotein; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin
keywords: Activator of G-protein signaling 3 (AGS3); CAMP response element (CRE)-binding protein (CREB); Cyclic 3′, 5′-adenosine monophosphate (cAMP); Dental pulp stem cells (DPSCs); Osteogenic differentiation; Protein kinase A (PKA); Tumor necrosis factor α (TNF-α)