ArticleThe Journal of cell biology2000
Signaling by fibroblast growth factors (FGF) and fibroblast growth factor receptor 2 (FGFR2)-activating mutations blocks mineralization and induces apoptosis in osteoblasts.
Article in The Journal of cell biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
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Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 296 citations in OpenAlex.
- Insights and future directions of potential genetic therapy for Apert syndrome: A systematic review.Gene therapy · 2021Pooled it
- FGF2-regulated Osteogenic Differentiation of Human Bone Marrow Stromal Cells.Current stem cell research & therapy · 2026Article
- Generation of human induced pluripotent stem cell lines from patients with FGFR2-linked syndromic craniosynostosis.Disease models & mechanisms · 2025Article
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- Further Evidence of Early-Onset Osteoporosis and Bone Fractures as a NewInternational journal of molecular sciences · 2025Article
- An FGFR2 mutation as the potential cause of a new phenotype including early-onset osteoporosis and bone fractures: a case report.BMC medical genomics · 2023Article
- Dental characteristics of patients with four different types of skeletal dysplasias.Clinical oral investigations · 2023Article
- Impact of FGF1 on human periodontal ligament fibroblast growth, osteogenic differentiation and inflammatory reaction in vitro.Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie · 2022Article
- Integrated DNA Copy Number and Expression Profiling Identifies IGF1R as a Prognostic Biomarker in Pediatric Osteosarcoma.International journal of molecular sciences · 2022Article
- Effect of Growth Hormone Therapy on a 4-Year-Old Girl with Pfeiffer Syndrome and Short Stature: A Case Report.Children (Basel, Switzerland) · 2022Article
- Protein tyrosine phosphatases in skeletal development and diseases.Bone research · 2022Review
- Article
- The Signalling Effects of Photobiomodulation on Osteoblast Proliferation, Maturation and Differentiation: A Review.Stem cell reviews and reports · 2021Review
- Review
- Targeted Ptpn11 deletion in mice reveals the essential role of SHP2 in osteoblast differentiation and skeletal homeostasis.Bone research · 2021Article
- 2b or Not 2b: How Opposing FGF Receptor Splice Variants Are Blocking Progress in Precision Oncology.Journal of oncology · 2021Review
- Cranial Neural Crest Cells and Their Role in the Pathogenesis of Craniofacial Anomalies and Coronal Craniosynostosis.Journal of developmental biology · 2020Review
- Crosstalk Between Cancer Associated Fibroblasts and Cancer Cells in Scirrhous Type Gastric Cancer.Frontiers in oncology · 2020Review
- Priming Dental Pulp Stem Cells from Human Exfoliated Deciduous Teeth with Fibroblast Growth Factor-2 Enhances Mineralization Within Tissue-Engineered Constructs Implanted in Craniofacial Bone Defects.Stem cells translational medicine · 2019Article
- The association of genetic variants inBioscience reports · 2019Article
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Fibroblast growth factors (FGF) play a critical role in bone growth and development affecting both chondrogenesis and osteogenesis. During the process of intramembranous ossification, which leads to the formation of the flat bones of the skull, unregulated FGF signaling can produce premature suture closure or craniosynostosis and other craniofacial deformities. Indeed, many human craniosynostosis disorders have been linked to activating mutations in FGF receptors (FGFR) 1 and 2, but the precise effects of FGF on the proliferation, maturation and differentiation of the target osteoblastic cells are still unclear. In this report, we studied the effects of FGF treatment on primary murine calvarial osteoblast, and on OB1, a newly established osteoblastic cell line. We show that FGF signaling has a dual effect on osteoblast proliferation and differentiation. FGFs activate the endogenous FGFRs leading to the formation of a Grb2/FRS2/Shp2 complex and activation of MAP kinase. However, immature osteoblasts respond to FGF treatment with increased proliferation, whereas in differentiating cells FGF does not induce DNA synthesis but causes apoptosis. When either primary or OB1 osteoblasts are induced to differentiate, FGF signaling inhibits expression of alkaline phosphatase, and blocks mineralization. To study the effect of craniosynostosis-linked mutations in osteoblasts, we introduced FGFR2 carrying either the C342Y (Crouzon syndrome) or the S252W (Apert syndrome) mutation in OB1 cells. Both mutations inhibited differentiation, while dramatically inducing apoptosis. Furthermore, we could also show that overexpression of FGF2 in transgenic mice leads to increased apoptosis in their calvaria. These data provide the first biochemical analysis of FGF signaling in osteoblasts, and show that FGF can act as a cell death inducer with distinct effects in proliferating and differentiating osteoblasts.
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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.