ArticlePLoS genetics2009
Mutations in GDF5 reveal a key residue mediating BMP inhibition by NOGGIN.
Article in PLoS genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 96 citations in OpenAlex.
- TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease.Bone research · 2026Review
- Understanding of the different roles of Noggin in the Noggin-BMP-2 and Noggin-BMP-9 dimer complexes at the molecular level.Scientific reports · 2026Article
- Endoglin as a BMP9 co-receptor in vascular endothelial cells: prodomain displacement and TGFBRII recruitment.Nature communications · 2025Article
- Gut-X Axis and Its Role in Poultry Bone Health: A Review.Microorganisms · 2025Review
- Clinical Presentation and WES Analysis of a Large Iranian Pedigree in Five Successive Generation Affected to Sever Multiple Synostosis 2 (SYNS2, Farhud Type).Iranian journal of public health · 2024Article
- A missenseJOR spine · 2024Article
- Fibular Agenesis and Ball-Like Toes Mimicking Preaxial Polydactyly: Prenatal Presentation of Du Pan Syndrome.Molecular syndromology · 2023Article
- The versatility and paradox of BMP signaling in endothelial cell behaviors and blood vessel function.Cellular and molecular life sciences : CMLS · 2022Review
- Hyaline cartilage differentiation of fibroblasts in regeneration and regenerative medicine.Development (Cambridge, England) · 2022Article
- Article
- Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions.International journal of molecular sciences · 2020Review
- Mechanisms of synovial joint and articular cartilage development.Cellular and molecular life sciences : CMLS · 2019Review
- The TGFβ type I receptor TGFβRI functions as an inhibitor of BMP signaling in cartilage.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Antagonism of BMP signaling is insufficient to induce fibrous differentiation in primary sclerotome.Experimental cell research · 2019Article
- The BMP-2 mutant L51P: a BMP receptor IA binding-deficient inhibitor of noggin.Journal of bone and mineral metabolism · 2019Review
- BMP9 stimulates joint regeneration at digit amputation wounds in mice.Nature communications · 2019Article
- A NovelMolecular syndromology · 2019Article
- Morphogenetic mechanism of the acquisition of the dinosaur-type acetabulum.Royal Society open science · 2018Article
- TGF-β Family Signaling in Early Vertebrate Development.Cold Spring Harbor perspectives in biology · 2018Review
- Bone Morphogenetic Protein-Based Therapeutic Approaches.Cold Spring Harbor perspectives in biology · 2018Review
Corrections and comments
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Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
Abstract
Signaling output of bone morphogenetic proteins (BMPs) is determined by two sets of opposing interactions, one with heterotetrameric complexes of cell surface receptors, the other with secreted antagonists that act as ligand traps. We identified two mutations (N445K,T) in patients with multiple synostosis syndrome (SYM1) in the BMP-related ligand GDF5. Functional studies of both mutants in chicken micromass culture demonstrated a gain of function caused by a resistance to the BMP-inhibitor NOGGIN and an altered signaling effect. Residue N445, situated within overlapping receptor and antagonist interfaces, is highly conserved among the BMP family with the exception of BMP9 and BMP10, in which it is substituted with lysine. Like the mutant GDF5, both BMPs are insensitive to NOGGIN and show a high chondrogenic activity. Ectopic expression of BMP9 or the GDF5 mutants resulted in massive induction of cartilage in an in vivo chick model presumably by bypassing the feedback inhibition imposed by endogenous NOGGIN. Swapping residues at the mutation site alone was not sufficient to render Bmp9 NOG-sensitive; however, successive introduction of two additional substitutions imparted high to total sensitivity on customized variants of Bmp9. In conclusion, we show a new mechanism for abnormal joint development that interferes with a naturally occurring regulatory mechanism of BMP signaling.
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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.