ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019
BMP9 directly induces rapid GSK3-β phosphorylation in a Wnt-independent manner through class I PI3K-Akt axis in osteoblasts.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- FK506 enhances bone morphogenetic protein 9-induced cementoblast differentiation in human cementoblast-lineage cells.Odontology · 2026Article
- Dual Inhibition of GSK3 and JAK by BIO Suppresses Osteoblast Differentiation and Mineralization of Human Mesenchymal Cells.Current issues in molecular biology · 2026Article
- Glabridin Alleviates Oxidative Stress-Induced Osteoporosis by Targeting the Akt/NF-ĸB and Akt/GSK-3β Pathways.International journal of molecular sciences · 2025Article
- Enhanced Osteoinduction and Osteogenesis Promotion by Bovine Freeze-Dried Bone Combined withACS omega · 2025Article
- Recent advances in the multifaceted mechanisms of catalpol in treating osteoporosis.Frontiers in pharmacology · 2025Review
- BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/Stat3 pathway in mesenchymal stem cells.Genes & diseases · 2024Article
- 17β-Estradiol (E2) Activates Matrix Mineralization through Genomic/Nongenomic Pathways in MC3T3-E1 Cells.International journal of molecular sciences · 2024Article
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- The effect and mechanism of selenium supplementation on the proliferation capacity of bovine endometrial epithelial cells exposed to lipopolysaccharide in vitro under high cortisol background.Journal of animal science · 2024Article
- BMP-9 Improves the Osteogenic Differentiation Ability over BMP-2 through p53 Signaling In Vitro in Human Periosteum-Derived Cells.International journal of molecular sciences · 2023Article
- Identification of Maleimide-Fused Carbazoles as Novel Noncanonical Bone Morphogenetic Protein Synergizers.ACS pharmacology & translational science · 2023Article
- Matricellular Protein SMOC2 Potentiates BMP9-Induced Osteogenic Differentiation in Mesenchymal Stem Cells through the Enhancement of FAK/PI3K/AKT Signaling.Stem cells international · 2023Article
- Akt/mTOR integrate energy metabolism with Wnt signal to influence wound epithelium growth in Gekko Japonicus.Communications biology · 2022Article
- Article
- Enhanced bone formation of calvarial bone defects by low-intensity pulsed ultrasound and recombinant human bone morphogenetic protein-9: a preliminary experimental study in rats.Clinical oral investigations · 2021Article
- LiCl induces apoptosis via CHOP/NOXA/Mcl-1 axis in human choroidal melanoma cells.Cancer cell international · 2021Article
- Energy Metabolism During Osteogenic Differentiation: The Role of Akt.Stem cells and development · 2021Article
- Changes in mediators of pro-cell growth, senescence, and inflammation during murine gestation.American journal of reproductive immunology (New York, N.Y. : 1989) · 2020Article
- Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF.Cell death & disease · 2020Article
- TGFβ1 induces bone formation from BMP9-activated Bone Mesenchymal Stem Cells, with possible involvement of non-canonical pathways.International journal of medical sciences · 2020Article
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9 authors at 1 institution in 1 country.
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Abstract
Bone morphogenetic protein (BMP)9 has been reported to be the most potent BMP to induce bone formation. However, the details of BMP9-transduced intracellular signaling remain ambiguous. Here, we have investigated signal transduction mechanisms of BMP9 in comparison to BMP2, another potent inducer of bone formation, in osteoblasts. In a mouse osteoblast cell line, BMP9 induced higher mRNA levels of alkaline phosphatase (ALP) and runt-related transcription factor 2 (Runx2) than BMP2 within 2 h. Unlike BMP2, BMP9 induced rapid phosphorylation of glycogen synthase kinase 3-β (GSK3-β) and protein kinase B (Akt) and increased the cellular protein content of β-catenin. BMP9 moderately increased mRNA levels of several canonical Wingless-related integration site to lower degrees than BMP2. Furthermore, BMP9-induced GSK3-β phosphorylation was not inhibited by pretreatment with actinomycin D, cycloheximide, or Brefeldin A, indicating it is independent of Wnt protein secretion. BMP9-induced GSK3-β phosphorylation was abrogated by Akt or class I PI3K-specific inhibitors. Moreover, inactivation of GSK3-β by LiCl did not further promote ALP and Runx2 mRNA induction by BMP9 as significantly as that by BMP2. Notably, BMP9-induced GSK3-β phosphorylation was inhibited by small interfering RNA against endoglin and GIPC PDZ domain-containing family, member 1. Taken together, our present findings have indicated that BMP9 directly activates GSK3β-β-catenin signaling pathway through class I PI3K-Akt Axis in osteoblasts, which may be essential for the potent osteoinductive activity of BMP9.-Eiraku, N., Chiba, N., Nakamura, T., Amir, M. S., Seong, C.-H., Ohnishi, T., Kusuyama, J., Noguchi, K., Matsuguchi, T. BMP9 directly induces rapid GSK3-β phosphorylation in a Wnt-independent manner through class I PI3K-Akt axis in osteoblasts.
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