ArticleHuman molecular genetics2015
Mutant activated FGFR3 impairs endochondral bone growth by preventing SOX9 downregulation in differentiating chondrocytes.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP.British journal of clinical pharmacology · 2022Trial
- Achondroplasia treatments in children aged 5 and older.Molecular and cellular pediatrics · 2025Review
- Embryonic cranial cartilage defects in the Fgfr3Anatomical record (Hoboken, N.J. : 2007) · 2025Article
- Advances in the mechanism and therapies of achondroplasia.Genes & diseases · 2025Review
- Syndrome-informed phenotyping identifies a polygenic background for achondroplasia-like facial variation in the general population.Nature communications · 2024Article
- The IFITM5 mutation in osteogenesis imperfecta type V is associated with an ERK/SOX9-dependent osteoprogenitor differentiation defect.The Journal of clinical investigation · 2024Article
- Syndrome-informed phenotyping identifies a polygenic background for achondroplasia-like facial variation in the general population.bioRxiv : the preprint server for biology · 2023Article
- Article
- Candidate genes for obstructive sleep apnea in non-syndromic children with craniofacial dysmorphisms - a narrative review.Frontiers in pediatrics · 2023Review
- Review
- Integrated RNA-Seq Analysis Uncovers the Potential Mechanism of the "Kidney Governing Bones" Theory of TCM.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- The hypertrophic chondrocyte: To be or not to be.Histology and histopathology · 2021Review
- Molecular Mechanisms of Chondrocyte Proliferation and Differentiation.Frontiers in cell and developmental biology · 2021Review
- Deciphering the potential pharmaceutical mechanism of Guzhi Zengsheng Zhitongwan on rat bone and kidney based on the "kidney governing bone" theory.Journal of orthopaedic surgery and research · 2020Article
- SOX9 in cartilage development and disease.Current opinion in cell biology · 2019Review
- Suppressing UPR-dependent overactivation of FGFR3 signaling ameliorates SLC26A2-deficient chondrodysplasias.EBioMedicine · 2019Article
- Achondroplasia with SRY-positive 46, XX disorder of sex development: an extremely rare association.Endocrinology, diabetes & metabolism case reports · 2018Article
- Achondroplasia: Development, pathogenesis, and therapy.Developmental dynamics : an official publication of the American Association of Anatomists · 2017Review
- Chondrocyte FGFR3 Regulates Bone Mass by Inhibiting Osteogenesis.The Journal of biological chemistry · 2016Article
- Developmental Regulation of the Growth Plate and Cranial Synchondrosis.Journal of dental research · 2016Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast growth factor receptor 3 (FGFR3) plays a critical role in the control of endochondral ossification, and bone growth and mutations that cause hyperactivation of FGFR3 are responsible for a collection of developmental disorders that feature poor endochondral bone growth. FGFR3 is expressed in proliferating chondrocytes of the cartilaginous growth plate but also in chondrocytes that have exited the cell cycle and entered the prehypertrophic phase of chondrocyte differentiation. Achondroplasia disorders feature defects in chondrocyte proliferation and differentiation, and the defects in differentiation have generally been considered to be a secondary manifestation of altered proliferation. By initiating a mutant activated knockin allele of FGFR3 (FGFR3K650E) that causes Thanatophoric Dysplasia Type II (TDII) specifically in prehypertrophic chondrocytes, we show that mutant FGFR3 induces a differentiation block at this stage independent of any changes in proliferation. The differentiation block coincided with persistent expression of SOX9, the master regulator of chondrogenesis, and reducing SOX9 dosage allowed chondrocyte differentiation to proceed and significantly improved endochondral bone growth in TDII. These findings suggest that a proliferation-independent and SOX9-dependent differentiation block is a key driving mechanism responsible for poor endochondral bone growth in achondroplasia disorders caused by mutations in FGFR3.
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