ArticleThe Journal of cell biology2000
Matrix metalloproteinase 9 and vascular endothelial growth factor are essential for osteoclast recruitment into developing long bones.
Article in The Journal of cell biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 186 papers, 1 of them a synthesis that pooled it.
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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
186 citing papers in PubMed, 1 synthesis or guideline pooled it, 590 citations in OpenAlex.
- Insights into the mechanism of vascular endothelial cells on bone biology.Bioscience reports · 2021Pooled it
- Vascular-lymphatic dual circulation in bone health and disease: Mechanistic coupling and translational therapeutics.Journal of orthopaedic translation · 2026Review
- Exploring the causal relationship and pathogenesis of intracranial aneurysms with osteoporosis based on Mendelian randomization and bioinformatics study.Journal of bone and mineral metabolism · 2026Article
- The Interstitial Collagenases MMP13 and MMP14 Are Dispensable for the Early Onset of Skin Morphogenesis but Modulate Endochondral Ossification.The American journal of pathology · 2026Article
- Treatment of heterotopic ossification via inhibiting the MMP-2/CDH5 axis through oral delivery of network pharmacology-predicted Chinese medicine.Materials today. Bio · 2026Article
- Medullary cavity expansion is mediated by distinct cell populations during fetal bone development.Nature communications · 2026Article
- Bone matrix proteins: regulators of skeletal remodeling and repair.Journal of bone and mineral metabolism · 2026Review
- New Therapeutic Options Against Clinically Relevant Proteases in Cancer Progression.Mini reviews in medicinal chemistry · 2026Review
- Macrophage polarization regulates bone homeostasis: a potential etiology and therapy for postmenopausal osteoporosis.Frontiers in immunology · 2026Review
- Non-coding RNA modulation in osteoclasts and its implications for osteoblast lineage cell behavior in a co-culture system.Cell communication and signaling : CCS · 2025Article
- Article
- The Extensive Study of Magnesium Deficiency, 25-(OH) Vitamin D3, Inflammatory Markers, and Parathyroid Hormone in Relation to Bone Mineral Density in Iraqi Osteoporosis Patients: A Cross-Sectional Study.Health science reports · 2025Article
- Matrix Metalloproteinase-9 Enhances Osteoclastogenesis: Insights from Transgenic Rabbit Bone Marrow Models and In Vitro Studies.International journal of molecular sciences · 2025Article
- The mechanisms and applications of endothelial progenitor cell therapy in the treatment of intracranial aneurysm.Journal of translational medicine · 2025Review
- Biomechanical characteristics of frozen bone allografts after gene therapy-induced revascularization.Academia biology · 2025Article
- Beyond resorption: osteoclasts as drivers of bone formation.Cell regeneration (London, England) · 2024Review
- Endothelial Progenitor Cells: A Review of Molecular Mechanisms in the Pathogenesis and Endovascular Treatment of Intracranial Aneurysms.Neuromolecular medicine · 2024Review
- Article
- The role of magnesium in the pathogenesis of osteoporosis.Frontiers in endocrinology · 2024Review
- Treatment with an inhibitor of matrix metalloproteinase 9 or cathepsin K lengthens embryonic lower jaw bone.Orthodontics & craniofacial research · 2023Article
126 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Bone development requires the recruitment of osteoclast precursors from surrounding mesenchyme, thereby allowing the key events of bone growth such as marrow cavity formation, capillary invasion, and matrix remodeling. We demonstrate that mice deficient in gelatinase B/matrix metalloproteinase (MMP)-9 exhibit a delay in osteoclast recruitment. Histological analysis and specialized invasion and bone resorption models show that MMP-9 is specifically required for the invasion of osteoclasts and endothelial cells into the discontinuously mineralized hypertrophic cartilage that fills the core of the diaphysis. However, MMPs other than MMP-9 are required for the passage of the cells through unmineralized type I collagen of the nascent bone collar, and play a role in resorption of mineralized matrix. MMP-9 stimulates the solubilization of unmineralized cartilage by MMP-13, a collagenase highly expressed in hypertrophic cartilage before osteoclast invasion. Hypertrophic cartilage also expresses vascular endothelial growth factor (VEGF), which binds to extracellular matrix and is made bioavailable by MMP-9 (Bergers, G., R. Brekken, G. McMahon, T.H. Vu, T. Itoh, K. Tamaki, K. Tanzawa, P. Thorpe, S. Itohara, Z. Werb, and D. Hanahan. 2000. Nat. Cell Biol. 2:737-744). We show that VEGF is a chemoattractant for osteoclasts. Moreover, invasion of osteoclasts into the hypertrophic cartilage requires VEGF because it is inhibited by blocking VEGF function. These observations identify specific actions of MMP-9 and VEGF that are critical for early bone development.
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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.