ArticleBiochemical and biophysical research communications2016
Orai1 mediates osteogenic differentiation via BMP signaling pathway in bone marrow mesenchymal stem cells.
Article in Biochemical and biophysical research communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Orai1 is Required for Osteogenic Differentiation on Nanoparticulate Mineralized Collagen Glycosaminoglycan Materials.Macromolecular bioscience · 2025Article
- The role of calcium channels in osteoporosis and their therapeutic potential.Frontiers in endocrinology · 2024Review
- Convergence of Calcium Channel Regulation and Mechanotransduction in Skeletal Regenerative Biomaterial Design.Advanced healthcare materials · 2023Review
- Store-Operated CaJournal of clinical medicine · 2023Review
- Mechanisms Underlying Influence of Bioelectricity in Development.Frontiers in cell and developmental biology · 2022Review
- Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular CaFrontiers in cell and developmental biology · 2022Article
- Role of KInternational journal of molecular sciences · 2021Review
- Effect of MgClInternational journal of molecular sciences · 2021Article
- FOXQ1 promotes the osteogenic differentiation of bone mesenchymal stem cells via Wnt/β-catenin signaling by binding with ANXA2.Stem cell research & therapy · 2020Article
- Mmu_circ_003795 regulates osteoblast differentiation and mineralization in MC3T3‑E1 and MDPC23 by targeting COL15A1.Molecular medicine reports · 2020Article
- Calcium Homeostasis: A Potential Vicious Cycle of Bone Metastasis in Breast Cancers.Frontiers in oncology · 2020Review
- Pinoresinol promotes MC3T3‑E1 cell proliferation and differentiation via the cyclic AMP/protein kinase A signaling pathway.Molecular medicine reports · 2019Article
- The roles of Orai and Stim in bone health and disease.Cell calcium · 2019Review
- Genetic Manipulation of Calcium Release-Activated Calcium Channel 1 Modulates the Multipotency of Human Cartilage-Derived Mesenchymal Stem Cells.Journal of immunology research · 2019Article
- Deletion of Orai1 leads to bone loss aggravated with aging and impairs function of osteoblast lineage cells.Bone reports · 2018Article
- Clinical and Molecular Perspectives of Reparative Dentin Formation: Lessons Learned from Pulp-Capping Materials and the Emerging Roles of Calcium.Dental clinics of North America · 2017Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Orai1 is a pore-subunit of store-operated Ca(2+) release-activated Ca(2+) (CRAC) channel that mediates Ca(2+) influx in most non-excitable cells via store-operated Ca(2+) entry (SOCE) mechanism. We previously demonstrated that Orai1 is involved in mediating osteogenic potential of mesenchymal stem cells (MSCs), but the underlying mechanism of this function remains unknown. Here, we report that Orai1 mediates osteogenic differentiation via bone morphogenic protein (BMP) signaling pathway in bone marrow MSCs (BMSCs). In osteogenic conditions, BMSCs derived from wild-type mice underwent osteoblastic differentiation and induced mineralization as demonstrated by increased alkaline phosphatase activity and alizarin red S staining, respectively. The expression of Runx2, a master regulator of osteoblast differentiation, and osteogenic differentiation markers were markedly increased in wild-type BMSCs under osteogenic conditions. In contrast, osteogenic conditions failed to induce such effects in BMSCs derived from Orai1-deficient (Orai1(-/-)) mice, indicating that Orai1 is, in part, necessary for osteogenic differentiation of MSCs. We also found that BMP2 successfully induced phosphorylation of Smad1/5/8, the immediate effector molecules of BMP signaling, in wild-type BMSCs, but failed to do so in Orai1(-/-) BMSCs. Downstream target genes of BMP signaling pathway were consistently increased by osteogenic conditions in wild-type BMSCs, but not in Orai1(-/-) BMSCs, suggesting a novel molecular link between Orai1 and BMP signaling pathway in the osteogenic differentiation process. Further functional studies demonstrated that activation of BMP signaling rescues osteogenic differentiation capacity of Orai1(-/-) BMSCs. In conclusion, Orai1 regulates osteogenic differentiation through BMP signaling, and the Orai1-BMP signaling may be a possible therapeutic target for treating bone-related diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.