ArticleMolecular and cellular biology2009
Sustained platelet-derived growth factor receptor alpha signaling in osteoblasts results in craniosynostosis by overactivating the phospholipase C-gamma pathway.
Article in Molecular and cellular biology, 2009. 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, 58 citations in OpenAlex.
- Nf2/FGFR1/AKT axis directs cranial neural crest-derived skull morphogenesis via collagen synthesis and trafficking.JCI insight · 2025Article
- PDGFRα signaling regulates cartilage and fibrous tissue differentiation during synovial joint development.Nature communications · 2025Article
- Characterizing the role of Pdgfra in calvarial development.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Gene regulatory network from cranial neural crest cells to osteoblast differentiation and calvarial bone development.Cellular and molecular life sciences : CMLS · 2022Review
- Dynamic proteomic profiling of human periodontal ligament stem cells during osteogenic differentiation.Stem cell research & therapy · 2021Article
- Aberrant upregulation of CaSR promotes pathological new bone formation in ankylosing spondylitis.EMBO molecular medicine · 2020Article
- Mouse Models of Syndromic Craniosynostosis.Molecular syndromology · 2019Review
- Overexpression ofDisease models & mechanisms · 2018Article
- Dysregulated PDGFRα signaling alters coronal suture morphogenesis and leads to craniosynostosis through endochondral ossification.Development (Cambridge, England) · 2017Article
- STAT1 modulates tissue wasting or overgrowth downstream from PDGFRβ.Genes & development · 2017Article
- PDGFRβ regulates craniofacial development through homodimers and functional heterodimers with PDGFRα.Genes & development · 2016Article
- Fibroblast growth factor signaling in skeletal development and disease.Genes & development · 2015Review
- Kit transduced signals counteract erythroid maturation by MAPK-dependent modulation of erythropoietin signaling and apoptosis induction in mouse fetal liver.Cell death and differentiation · 2015Article
- Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies.Cellular and molecular life sciences : CMLS · 2015Review
- A new ultrasound method for assessment of head shape change in infants with plagiocephaly.Annals of rehabilitation medicine · 2014Article
- MAPK/ERK Signaling Pathway Analysis in Primary Osteoblasts From Patients With Nonsyndromic Sagittal Craniosynostosis.The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association · 2014Article
- The molecular and cellular basis of Apert syndrome.Intractable & rare diseases research · 2013Review
- Cranial sutures: a multidisciplinary review.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2013Review
- Phospholipases of mineralization competent cells and matrix vesicles: roles in physiological and pathological mineralizations.International journal of molecular sciences · 2013Article
- The role of vertebrate models in understanding craniosynostosis.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2012Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development and growth of the skull is controlled by cranial sutures, which serve as growth centers for osteogenesis by providing a pool of osteoprogenitors. These osteoprogenitors undergo intramembranous ossification by direct differentiation into osteoblasts, which synthesize the components of the extracellular bone matrix. A dysregulation of osteoblast differentiation can lead to premature fusion of sutures, resulting in an abnormal skull shape, a disease called craniosynostosis. Although several genes could be linked to craniosynostosis, the mechanisms regulating cranial suture development remain largely elusive. We have established transgenic mice conditionally expressing an autoactivated platelet-derived growth factor receptor alpha (PDGFRalpha) in neural crest cells (NCCs) and their derivatives. In these mice, premature fusion of NCC-derived sutures occurred at early postnatal stages. In vivo and in vitro experiments demonstrated enhanced proliferation of osteoprogenitors and accelerated ossification of osteoblasts. Furthermore, in osteoblasts expressing the autoactivated receptor, we detected an upregulation of the phospholipase C-gamma (PLC-gamma) pathway. Treatment of differentiating osteoblasts with a PLC-gamma-specific inhibitor prevented the mineralization of synthesized bone matrix. Thus, we show for the first time that PDGFRalpha signaling stimulates osteogenesis of NCC-derived osteoblasts by activating the PLC-gamma pathway, suggesting an involvement of this pathway in the etiology of human craniosynostosis.
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