ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2017
Rap1b Is an Effector of Axin2 Regulating Crosstalk of Signaling Pathways During Skeletal Development.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
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- Stem cell-associated osteogenic deficiency causes craniofacial deformities with progeroid accumulation of prelamin A.JCI insight · 2026Article
- p75 neurotrophin receptor regulates craniofacial growth and morphology in postnatal development.Frontiers in cell and developmental biology · 2025Article
- Acute exposure to electronic cigarette components alters mRNA expression of pre-osteoblasts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Proteomic Analysis Based on TMT Regarding the Therapeutic Action ofCombinatorial chemistry & high throughput screening · 2024Article
- Mesenchymal stem cells in craniofacial reconstruction: a comprehensive review.Frontiers in molecular biosciences · 2024Review
- A Simplified and Effective Approach for the Isolation of Small Pluripotent Stem Cells Derived from Human Peripheral Blood.Biomedicines · 2023Article
- miRNA-27a is essential for bone remodeling by modulating p62-mediated osteoclast signaling.eLife · 2023Article
- BMP signaling during craniofacial development: new insights into pathological mechanisms leading to craniofacial anomalies.Frontiers in physiology · 2023Review
- Differential regulation of skeletal stem/progenitor cells in distinct skeletal compartments.Frontiers in physiology · 2023Review
- GATA3 mediates nonclassical β-catenin signaling in skeletal cell fate determination and ectopic chondrogenesis.Science advances · 2022Article
- Krüppel-like factor-4 and Krüppel-like factor-2 are important regulators of joint tissue cells and protect against tissue destruction and inflammation in osteoarthritis.Annals of the rheumatic diseases · 2022Article
- Comparison of Gene Expression Patterns in Articular Cartilage and Xiphoid Cartilage.Biochemical genetics · 2022Article
- Effect of Regulator of G Protein Signaling Proteins on Bone.Frontiers in endocrinology · 2022Review
- New perspective of skeletal stem cells.Biomaterials translational · 2022Review
- Fetal Immunomodulatory Environment Following Cartilage Injury-The Key to CARTILAGE Regeneration?International journal of molecular sciences · 2021Article
- Cranial Suture Mesenchymal Stem Cells: Insights and Advances.Biomolecules · 2021Review
- BMPR1A maintains skeletal stem cell properties in craniofacial development and craniosynostosis.Science translational medicine · 2021Article
- Screening of differentially expressed miRNAs during osteogenic/odontogenic differentiation of human dental pulp stem cells exposed to mechanical stress.American journal of translational research · 2021Article
- GLI1 and AXIN2 Are Distinctive Markers of Human Calvarial Mesenchymal Stromal Cells in Nonsyndromic Craniosynostosis.International journal of molecular sciences · 2020Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Recent identification and isolation of suture stem cells capable of long-term self-renewal, clonal expanding, and differentiating demonstrate their essential role in calvarial bone development, homeostasis, and injury repair. These bona fide stem cells express a high level of Axin2 and are able to mediate bone regeneration and repair in a cell autonomous fashion. The importance of Axin2 is further demonstrated by its genetic inactivation in mice causing skeletal deformities resembling craniosynostosis in humans. The fate determination and subsequent differentiation of Axin2+ stem cells are highly orchestrated by a variety of evolutionary conserved signaling pathways including Wnt, FGF, and BMP. These signals are often antagonistic of each other and possess differential effects on osteogenic and chondrogenic cell types. However, the mechanisms underlying the interplay of these signaling transductions remain largely elusive. Here we identify Rap1b acting downstream of Axin2 as a signaling interrogator for FGF and BMP. Genetic analysis reveals that Rap1b is essential for development of craniofacial and body skeletons. Axin2 regulates Rap1b through modulation of canonical BMP signaling. The BMP-mediated activation of Rap1b promotes chondrogenic fate and chondrogenesis. Furthermore, by inhibiting MAPK signaling, Rap1b mediates the antagonizing effect of BMP on FGF to repress osteoblast differentiation. Disruption of Rap1b in mice not only enhances osteoblast differentiation but also impairs chondrocyte differentiation during intramembranous and endochondral ossifications, respectively, leading to severe defects in craniofacial and body skeletons. Our findings reveal a dual role of Rap1b in development of the skeletogenic cell types. Rap1b is critical for balancing the signaling effects of BMP and FGF during skeletal development and disease. © 2017 American Society for Bone and Mineral Research.
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Registered trials
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