ArticlePLoS genetics2017
Unsuspected osteochondroma-like outgrowths in the cranial base of Hereditary Multiple Exostoses patients and modeling and treatment with a BMP antagonist in mice.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG).International journal of molecular sciences · 2022Pooled it
- Article
- Orthopedic preoperative evaluation and surgical strategies of hereditary multiple osteochondromas involving the spinal region.EFORT open reviews · 2026Review
- Enhanced BMP Signaling Alters Human β-Cell Identity and Function.Advanced biology · 2025Article
- Free glutaraldehyde gelatin microsphere loaded mesenchymal stem cells alleviate osteoarthritis by promotingTheranostics · 2025Article
- Costal chondrosarcoma in a woman with hereditary multiple exostoses - a case report.Frontiers in oncology · 2025Article
- Analysis of the Actions of RARγ Agonists on Growing Osteochondromas in a Mouse Model.International journal of molecular sciences · 2024Article
- Palovarotene Action Against Heterotopic Ossification Includes a Reduction of Local Participating Activin A-Expressing Cell Populations.JBMR plus · 2023Article
- Article
- Osteochondroma formation is independent of heparanase expression as revealed in a mouse model of hereditary multiple exostoses.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2022Article
- Clinical survey of a pedigree with hereditary multiple exostoses and identification of EXT‑2 gene deletion mutation.Molecular medicine reports · 2022Article
- Osteochondroma Pathogenesis: Mouse Models and Mechanistic Insights into Interactions with Retinoid Signaling.The American journal of pathology · 2021Review
- Localized chondro-ossification underlies joint dysfunction and motor deficits in theProceedings of the National Academy of Sciences of the United States of America · 2021Article
- A vertebrate adaptive radiation is assembled from an ancient and disjunct spatiotemporal landscape.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Endoscopic endonasal extreme far-medial approach for a lower clivus osteochondroma in a patient with hereditary multiple exostoses: illustrative case.Journal of neurosurgery. Case lessons · 2021Article
- Hereditary Multiple Exostoses-A Review of the Molecular Background, Diagnostics, and Potential Therapeutic Strategies.Frontiers in genetics · 2021Review
- Heparan sulfate deficiency leads to hypertrophic chondrocytes by increasing bone morphogenetic protein signaling.Osteoarthritis and cartilage · 2020Article
- Lactococcus Lactis Subsp. cremoris Is an Efficacious Beneficial Bacterium that Limits Tissue Injury in the Intestine.iScience · 2019Article
- Hereditary Multiple Exostoses: Current Insights.Orthopedic research and reviews · 2019Review
- The pathogenic roles of heparan sulfate deficiency in hereditary multiple exostoses.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Hereditary Multiple Exostoses (HME) is a rare pediatric disorder caused by loss-of-function mutations in the genes encoding the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2. HME is characterized by formation of cartilaginous outgrowths-called osteochondromas- next to the growth plates of many axial and appendicular skeletal elements. Surprisingly, it is not known whether such tumors also form in endochondral elements of the craniofacial skeleton. Here, we carried out a retrospective analysis of cervical spine MRI and CT scans from 50 consecutive HME patients that included cranial skeletal images. Interestingly, nearly half of the patients displayed moderate defects or osteochondroma-like outgrowths in the cranial base and specifically in the clivus. In good correlation, osteochondromas developed in the cranial base of mutant Ext1f/f;Col2-CreER or Ext1f/f;Aggrecan-CreER mouse models of HME along the synchondrosis growth plates. Osteochondroma formation was preceded by phenotypic alteration of cells at the chondro-perichondrial boundary and was accompanied by ectopic expression of major cartilage matrix genes -collagen 2 and collagen X- within the growing ectopic masses. Because chondrogenesis requires bone morphogenetic protein (BMP) signaling, we asked whether osteochondroma formation could be blocked by a BMP signaling antagonist. Systemic administration with LDN-193189 effectively inhibited osteochondroma growth in conditional Ext1-mutant mice. In vitro studies with mouse embryo chondrogenic cells clarified the mechanisms of LDN-193189 action that turned out to include decreases in canonical BMP signaling pSMAD1/5/8 effectors but interestingly, concurrent increases in such anti-chondrogenic mechanisms as pERK1/2 and Chordin, Fgf9 and Fgf18 expression. Our study is the first to reveal that the cranial base can be affected in patients with HME and that osteochondroma formation is amenable to therapeutic drug intervention.
Indexed as
Identifiers
What OpenQuestion holds
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.