ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2017
Lymphatic Endothelial Cells Produce M-CSF, Causing Massive Bone Loss in Mice.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2017. 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 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Insights into the mechanism of vascular endothelial cells on bone biology.Bioscience reports · 2021Pooled it
- Article
- Blood and lymphatic vascular network in bone injury repair: from molecular mechanisms to therapeutic strategies.Science China. Life sciences · 2026Review
- Therapeutic Efficacy of Sirolimus in Skeletal Manifestations of Gorham-Stout Disease in Adults: A Systematic Review.Cureus · 2026Review
- VEGF-D-induced intraosseous lymphangiogenesis drives site-specific heterotopic bone resorption.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Breaking down to rebuild: lymphatic ablation enhances osteoclast-driven regeneration.The Journal of clinical investigation · 2026Article
- Lymphatic vascular aging and age-related bone loss: current status and future perspectives.Frontiers in immunology · 2026Review
- Crosstalk between lymphatic system and synovial inflammatory cells in osteoarthritis: molecular mechanisms and potential cell-based therapies.Journal of translational medicine · 2025Review
- Reduced expression of semaphorin 3A in osteoclasts causes lymphatic expansion in a Gorham-Stout disease (GSD) mouse model.Journal of Zhejiang University. Science. B · 2024Article
- The role of vascular and lymphatic networks in bone and joint homeostasis and pathology.Frontiers in endocrinology · 2024Review
- CSF-1 and Notch signaling cooperate in macrophage instruction and tissue repair during peripheral limb ischemia.Frontiers in immunology · 2023Article
- The molecular mechanism of Gorham syndrome: an update.Frontiers in immunology · 2023Review
- Difficult Therapeutic Decisions in Gorham-Stout Disease-Case Report and Review of the Literature.International journal of environmental research and public health · 2022Review
- Gorham-Stout disease, a diagnosis of exclusion.Radiology case reports · 2022Article
- Osteopathy in Complex Lymphatic Anomalies.International journal of molecular sciences · 2022Review
- The importance of computed tomography (CT) scans in the early diagnosis of Gorham-Stout Disease - A case report.Radiology case reports · 2022Article
- Current concepts from diagnosis to management in Gorham-Stout disease: a systematic narrative review of about 350 cases.EFORT open reviews · 2022Review
- The endothelium-bone axis in development, homeostasis and bone and joint disease.Nature reviews. Rheumatology · 2021Review
- Lymphatic muscle cells contribute to dysfunction of the synovial lymphatic system in inflammatory arthritis in mice.Arthritis research & therapy · 2021Article
- Lymphatics in bone arise from pre-existing lymphatics.Development (Cambridge, England) · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Gorham-Stout disease (GSD) is a rare bone disorder characterized by aggressive osteolysis associated with lymphatic vessel invasion within bone marrow cavities. The etiology of GSD is not known, and there is no effective therapy or animal model for the disease. Here, we investigated if lymphatic endothelial cells (LECs) affect osteoclasts (OCs) to cause a GSD osteolytic phenotype in mice. We examined the effect of a mouse LEC line on osteoclastogenesis in co-cultures. LECs significantly increased receptor activator of NF-κB ligand (RANKL)-mediated OC formation and bone resorption. LECs expressed high levels of macrophage colony-stimulating factor (M-CSF), but not RANKL, interleukin-6 (IL-6), and tumor necrosis factor (TNF). LEC-mediated OC formation and bone resorption were blocked by an M-CSF neutralizing antibody or Ki20227, an inhibitor of the M-CSF receptor, c-Fms. We injected LECs into the tibias of wild-type (WT) mice and observed massive osteolysis on X-ray and micro-CT scans. Histology showed that LEC-injected tibias had significant trabecular and cortical bone loss and increased OC numbers. M-CSF protein levels were significantly higher in serum and bone marrow plasma of mice given intra-tibial LEC injections. Immunofluorescence staining showed extensive replacement of bone and marrow by podoplanin+ LECs. Treatment of LEC-injected mice with Ki20227 significantly decreased tibial bone destruction. In addition, lymphatic vessels in a GSD bone sample were stained positively for M-CSF. Thus, LECs cause bone destruction in vivo in mice by secreting M-CSF, which promotes OC formation and activation. Blocking M-CSF signaling may represent a new therapeutic approach for treatment of patients with GSD. Furthermore, tibial injection of LECs is a useful mouse model to study GSD. © 2017 American Society for Bone and Mineral Research.
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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.