Less Vertebral Bone Mass after Treatment with Macitentan in Mice: A Pilot Study.

Purpose. Blood vessels and skeleton interact together. Endothelin-1 is a potent vasoconstrictor and also has an effect on bone metabolism. The dual antagonist to both endothelin-1 type A and B receptors, Macitentan, has been approved for clinical management of pulmonary arterial hypertension while l...

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Publicado en:BioMed Research International pp. 1 - 7
Autores principales: Liu, Zhong-Yu, Au, Man-Ting, He, Tian-Wei, Yang, Bu, Liu, Bin, Zhang, Liang-Ming, Luo, Chun-Xiao, Rong, Li-Min, Wen, Chun-Yi
Formato: diagnostic images pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 2/19/2019
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2/19/2019
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2019/2075968
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        atl: Less Vertebral Bone Mass after Treatment with Macitentan in Mice: A Pilot Study.
      aug:
        au:
          Liu, Zhong-Yu
          Au, Man-Ting
          He, Tian-Wei
          Yang, Bu
          Liu, Bin
          Zhang, Liang-Ming
          Luo, Chun-Xiao
          Rong, Li-Min
          Wen, Chun-Yi
        affil: Department of Spine Surgery, Institute of Drug Clinical Trial for Orthopedic Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
      sug:
        subj:
          Receptors, Cell Surface Antagonists and Inhibitors
          Bone Density Drug Effects
          Receptors, Cell Surface Pharmacodynamics
          Spine Drug Effects
          Endothelins Pharmacodynamics
          Endothelins Antagonists and Inhibitors
          Animal Studies
          Mice
          Molecular Structure
          Pilot Studies
          Administration, Intraperitoneal
          Receptors, Cell Surface Administration and Dosage
          Endothelins Blood
          Enzyme-Linked Immunosorbent Assay
          Tomography, X-Ray Computed Methods
          Histological Techniques Methods
          Osteoblasts
          Cancellous Bone
          Immunohistochemistry
          Biological Markers
      ab: Purpose. Blood vessels and skeleton interact together. Endothelin-1 is a potent vasoconstrictor and also has an effect on bone metabolism. The dual antagonist to both endothelin-1 type A and B receptors, Macitentan, has been approved for clinical management of pulmonary arterial hypertension while little is known about the secondary effect of the drug on spine. We aimed to answer how vertebral bone mass responded to Macitentan treatment in mice. Methods. Sixteen male balb/c mice at 6 months were randomly assigned into 2 groups. Vehicle and Macitentan were administrated via intraperitoneal injection to Control group and Treatment group, respectively, for 4 months. At sacrifice, plasma endothelin-1 was evaluated with ELISA and vertebral bone mass was evaluated with Microcomputed Tomography and histological analysis. Results. We found higher plasma endothelin-1 level (p<0.01) and less vertebral bone mass (p<0.05) in Treatment group compared to controls. Moreover, less osteoblasts and more osteoclasts were observed in the vertebral trabecular bone in the Treatment group compared to controls, by immunohistochemistry of the cell-specific markers. Conclusions. Treatment with Macitentan is associated with significant lower vertebral bone mass and therefore the secondary effect of dual antagonists to endothelin-1 receptors on the skeleton should be monitored and investigated in clinical practice. Both osteoblasts and osteoclasts may be involved while the molecular mechanism needs to be further explored.
      pubtype: Academic Journal
      doctype:
        diagnostic images
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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