ArticleMatrix biology : journal of the International Society for Matrix Biology2012
Perlecan modulates VEGF signaling and is essential for vascularization in endochondral bone formation.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 80 citations in OpenAlex.
- The regulatory significance of chondrocyte hypertrophy in maintaining chondrocyte homeostasis, regeneration and repair.Future science OA · 2026Review
- The developmental remodeling front: resorptive cell-vascular coupling at the chondro-osseous junction.Frontiers in cell and developmental biology · 2026Review
- Distinct role of perlecan in mesenchymal tissue regeneration via genetic and epigenetic modification.Chemical engineering journal (Lausanne, Switzerland : 1996) · 2025Article
- Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics.International journal of experimental pathology · 2025Review
- HSPG2 could promote normal haematopoiesis in acute myeloid leukaemia patients after complete remission by repairing bone marrow endothelial progenitor cells.Clinical and translational medicine · 2025Article
- Perlecan: a review of its role in neurologic and musculoskeletal disease.Frontiers in physiology · 2023Review
- The role of proteoglycan form of DMP1 in cranial repair.BMC molecular and cell biology · 2022Article
- Review
- Influence of light supplement on duck sternal calcification from integrated analysis of metabolome and transcriptome.Poultry science · 2022Article
- Perlecan, A Multi-Functional, Cell-Instructive, Matrix-Stabilizing Proteoglycan With Roles in Tissue Development Has Relevance to Connective Tissue Repair and Regeneration.Frontiers in cell and developmental biology · 2022Review
- Developmental Transcriptome Profiling of the Tibial Reveals the Underlying Molecular Basis for Why Newly Hatched Quails Can Walk While Newly Hatched Pigeons Cannot.Frontiers in cell and developmental biology · 2022Article
- Increased Risk of Aortic Dissection with Perlecan Deficiency.International journal of molecular sciences · 2021Article
- Scientific Developments and Clinical Applications Utilizing Chondrons and Chondrocytes with Matrix for Cartilage Repair.Cartilage · 2021Review
- Impact of perlecan, a core component of basement membrane, on regeneration of cartilaginous tissues.Acta biomaterialia · 2021Review
- 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
- Proteoglycans and Glycosaminoglycans in Stem Cell Homeostasis and Bone Tissue Regeneration.Frontiers in cell and developmental biology · 2021Review
- GPN-1/glypican and UNC-52/perlecan do not appear to function in BMP signaling to pattern themicroPublication biology · 2021Article
- Review
- Perlecan Knockdown Significantly Alters Extracellular Matrix Composition and Organization During Cartilage Development.Molecular & cellular proteomics : MCP · 2020Article
- Trabecular Bone Deficit and Enhanced Anabolic Response to Re-Ambulation after Disuse in Perlecan-Deficient Skeleton.Biomolecules · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Perlecan (Hspg2) is a heparan sulfate proteoglycan expressed in basement membranes and cartilage. Perlecan deficiency (Hspg2(-/-)) in mice and humans causes lethal chondrodysplasia, which indicates that perlecan is essential for cartilage development. However, the function of perlecan in endochondral ossification is not clear. Here, we report the critical role of perlecan in VEGF signaling and angiogenesis in growth plate formation. The Hspg2(-/-) growth plate was significantly wider but shorter due to severely impaired endochondral bone formation. Hypertrophic chondrocytes were differentiated in Hspg2(-/-) growth plates; however, removal of the hypertrophic matrix and calcified cartilage was inhibited. Although the expression of MMP-13, CTGF, and VEGFA was significantly upregulated in Hspg2(-/-) growth plates, vascular invasion into the hypertrophic zone was impaired, which resulted in an almost complete lack of bone marrow and trabecular bone. We demonstrated that cartilage perlecan promoted activation of VEGF/VEGFR by binding to the VEGFR of endothelial cells. Expression of the perlecan transgene specific to the cartilage of Hspg2(-/-) mice rescued their perinatal lethality and growth plate abnormalities, and vascularization into the growth plate was restored, indicating that perlecan in the growth plate, not in endothelial cells, is critical in this process. These results suggest that perlecan in cartilage is required for activating VEGFR signaling of endothelial cells for vascular invasion and for osteoblast migration into the growth plate. Thus, perlecan in cartilage plays a critical role in endochondral bone formation by promoting angiogenesis essential for cartilage matrix remodeling and subsequent endochondral bone formation.
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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.