ArticleBone2013
Epiphyseal abnormalities, trabecular bone loss and articular chondrocyte hypertrophy develop in the long bones of postnatal Ext1-deficient mice.
Article in Bone, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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
29 citing papers in PubMed, 44 citations in OpenAlex.
- Generation of Ext1 Gene-Edited Mice Model Via Dual sgRNAs/Cas9 System and Phenotypic Analyses.Molecular biotechnology · 2025Article
- Free glutaraldehyde gelatin microsphere loaded mesenchymal stem cells alleviate osteoarthritis by promotingTheranostics · 2025Article
- Interleukin-34 orchestrates bone formation through its binding to bone morphogenic proteins.Theranostics · 2025Article
- Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses.International journal of molecular sciences · 2022Review
- Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation.International journal of molecular sciences · 2022Review
- Osteochondroma Pathogenesis: Mouse Models and Mechanistic Insights into Interactions with Retinoid Signaling.The American journal of pathology · 2021Review
- Heparan Sulfate Deficiency in Cartilage: Enhanced BMP-Sensitivity, Proteoglycan Production and an Anti-Apoptotic Expression Signature after Loading.International journal of molecular sciences · 2021Article
- Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses.Orphanet journal of rare diseases · 2021Article
- Heparan sulfate deficiency leads to hypertrophic chondrocytes by increasing bone morphogenetic protein signaling.Osteoarthritis and cartilage · 2020Article
- An altered heparan sulfate structure in the articular cartilage protects against osteoarthritis.Osteoarthritis and cartilage · 2020Article
- The pathogenic roles of heparan sulfate deficiency in hereditary multiple exostoses.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- Heparan sulfate antagonism alters bone morphogenetic protein signaling and receptor dynamics, suggesting a mechanism in hereditary multiple exostoses.The Journal of biological chemistry · 2018Article
- Article
- Hereditary multiple exostoses: are there new plausible treatment strategies?Expert opinion on orphan drugs · 2018Article
- Advances in the pathogenesis and possible treatments for multiple hereditary exostoses from the 2016 international MHE conference.Connective tissue research · 2018Article
- Aberrant perichondrial BMP signaling mediates multiple osteochondromagenesis in mice.JCI insight · 2017Article
- Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments.Current osteoporosis reports · 2017Review
- Physeal histological morphology after thermal epiphysiodesis using radiofrequency ablation.Journal of orthopaedics and traumatology : official journal of the Italian Society of Orthopaedics and Traumatology · 2017Article
- Unsuspected osteochondroma-like outgrowths in the cranial base of Hereditary Multiple Exostoses patients and modeling and treatment with a BMP antagonist in mice.PLoS genetics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Long bones are integral components of the limb skeleton. Recent studies have indicated that embryonic long bone development is altered by mutations in Ext genes and consequent heparan sulfate (HS) deficiency, possibly due to changes in activity and distribution of HS-binding/growth plate-associated signaling proteins. Here we asked whether Ext function is continuously required after birth to sustain growth plate function and long bone growth and organization. Compound transgenic Ext1(f/f);Col2CreERT mice were injected with tamoxifen at postnatal day 5 (P5) to ablate Ext1 in cartilage and monitored over time. The Ext1-deficient mice exhibited growth retardation already by 2weeks post-injection, as did their long bones. Mutant growth plates displayed a severe disorganization of chondrocyte columnar organization, a shortened hypertrophic zone with low expression of collagen X and MMP-13, and reduced primary spongiosa accompanied, however, by increased numbers of TRAP-positive osteoclasts at the chondro-osseous border. The mutant epiphyses were abnormal as well. Formation of a secondary ossification center was significantly delayed but interestingly, hypertrophic-like chondrocytes emerged within articular cartilage, similar to those often seen in osteoarthritic joints. Indeed, the cells displayed a large size and round shape, expressed collagen X and MMP-13 and were surrounded by an abundant Perlecan-rich pericellular matrix not seen in control articular chondrocytes. In addition, ectopic cartilaginous outgrowths developed on the lateral side of mutant growth plates over time that resembled exostotic characteristic of children with Hereditary Multiple Exostoses, a syndrome caused by Ext mutations and HS deficiency. In sum, the data do show that Ext1 is continuously required for postnatal growth and organization of long bones as well as their adjacent joints. Ext1 deficiency elicits defects that can occur in human skeletal conditions including trabecular bone loss, osteoarthritis and HME.
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.