ArticleThe American journal of pathology2015
Heparanase stimulates chondrogenesis and is up-regulated in human ectopic cartilage: a mechanism possibly involved in hereditary multiple exostoses.
Article in The American journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Orthopedic preoperative evaluation and surgical strategies of hereditary multiple osteochondromas involving the spinal region.EFORT open reviews · 2026Review
- The Role of Heparan Sulfate in Bone Repair and Regeneration.Calcified tissue international · 2025Review
- Review
- 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
- Regulation of FGF-2, FGF-18 and Transcription Factor Activity by Perlecan in the Maturational Development of Transitional Rudiment and Growth Plate Cartilages and in the Maintenance of Permanent Cartilage Homeostasis.International journal of molecular sciences · 2022Review
- Perlecan in the Natural and Cell Therapy Repair of Human Adult Articular Cartilage: Can Modifications in This Proteoglycan Be a Novel Therapeutic Approach?Biomolecules · 2021Article
- Hereditary Multiple Exostoses-A Review of the Molecular Background, Diagnostics, and Potential Therapeutic Strategies.Frontiers in genetics · 2021Review
- Review
- 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
- Hereditary Multiple Exostoses: Current Insights.Orthopedic research and reviews · 2019Review
- Domains with highest heparan sulfate-binding affinity reside at opposite ends in BMP2/4The Journal of biological chemistry · 2018Article
- Heparan sulfate antagonism alters bone morphogenetic protein signaling and receptor dynamics, suggesting a mechanism in hereditary multiple exostoses.The Journal of biological chemistry · 2018Article
- Advances in the pathogenesis and possible treatments for multiple hereditary exostoses from the 2016 international MHE conference.Connective tissue research · 2018Article
- Hereditary multiple exostoses: are there new plausible treatment strategies?Expert opinion on orphan drugs · 2018Article
- The Good the Bad and the Ugly of Glycosaminoglycans in Tissue Engineering Applications.Pharmaceuticals (Basel, Switzerland) · 2017Review
- Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments.Current osteoporosis reports · 2017Review
- 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
- Extracellular Matrix Mediates BMP-2 in a Model of Temporomandibular Joint Osteoarthritis.Cells, tissues, organs · 2017Article
- Inhibition of connexin 43 prevents trauma-induced heterotopic ossification.Scientific reports · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
Hereditary multiple exostoses is a pediatric skeletal disorder characterized by benign cartilaginous tumors called exostoses that form next to growing skeletal elements. Hereditary multiple exostoses patients carry heterozygous mutations in the heparan sulfate (HS)-synthesizing enzymes EXT1 or EXT2, but studies suggest that EXT haploinsufficiency and ensuing partial HS deficiency are insufficient for exostosis formation. Searching for additional pathways, we analyzed presence and distribution of heparanase in human exostoses. Heparanase was readily detectable in most chondrocytes, particularly in cell clusters. In control growth plates from unaffected persons, however, heparanase was detectable only in hypertrophic zone. Treatment of mouse embryo limb mesenchymal micromass cultures with exogenous heparanase greatly stimulated chondrogenesis and bone morphogenetic protein signaling as revealed by Smad1/5/8 phosphorylation. It also stimulated cell migration and proliferation. Interfering with HS function both with the chemical antagonist Surfen or treatment with bacterial heparitinase up-regulated endogenous heparanase gene expression, suggesting a counterintuitive feedback mechanism that would result in further HS reduction and increased signaling. Thus, we tested a potent heparanase inhibitor (SST0001), which strongly inhibited chondrogenesis. Our data clearly indicate that heparanase is able to stimulate chondrogenesis, bone morphogenetic protein signaling, cell migration, and cell proliferation in chondrogenic cells. These properties may allow heparanase to play a role in exostosis genesis and pathogenesis, thus making it a conceivable therapeutic target in hereditary multiple exostoses.
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