10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Lymphatic endothelial cells produce M-CSF causing massive bone loss in mice

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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 RANKL-mediated OC formation and bone resorption. LECs expressed high levels of M-CSF, but not RANKL, IL-6 and TNF. LEC-mediated OC formation and bone resorption were blocked by an M-CSF neutralizing antibody or Ki20227, a inhibitor of the M-CSF receptor, c-Fms. We injected LECs into the tibiae of WT mice and observed massive osteolysis on X-ray and micro-CT scans. Histology showed that LEC-injected tibiae 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.

          Related collections

          Author and article information

          Journal
          8610640
          104
          J Bone Miner Res
          J. Bone Miner. Res.
          Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
          0884-0431
          1523-4681
          7 January 2017
          31 January 2017
          May 2017
          01 May 2018
          : 32
          : 5
          : 939-950
          Affiliations
          [1 ]The 1 st affiliated hospital, Xinxiang Medical University, Xinxiang 453000, China
          [2 ]Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, USA
          [3 ]Center for Musculoskeletal Research, University of Rochester Medical Center, USA
          [4 ]Institute of Stomatology, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China
          [5 ]Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
          Author notes
          [# ]Corresponding author: Lianping Xing, Department of Pathology and Laboratory Medicine, 601 Elmwood Ave, Box 626, Rochester, NY 14642, USA. Phone (585) 273-4090, Fax (585) 756-4468, Lianping_xing@ 123456urmc.rochester.edu
          [*]

          These authors made equal contribution to this work.

          Article
          PMC5413433 PMC5413433 5413433 nihpa840901
          10.1002/jbmr.3077
          5413433
          28052488
          ed01dbe5-4dfa-4a5a-8968-c5dcca872e82
          History
          Categories
          Article

          osteoclasts,Gorham-Stout disease,lymphatic endothelial cells,M-CSF,bone resorption

          Comments

          Comment on this article