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Title: Less vertebral bone mass after treatment with macitentan in mice : a pilot study
Authors: Liu, ZY
Au, MT 
He, TW
Yang, B
Liu, B
Zhang, LM
Luo, CX
Rong, LM
Wen, CY 
Issue Date: 2019
Publisher: Hindawi Publishing Corporation
Source: BioMed research international, 2019, 2075968, p. 1-6 How to cite?
Journal: BioMed research international 
Abstract: 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.
ISSN: 2314-6133
EISSN: 2314-6141
DOI: 10.1155/2019/2075968
Rights: Copyright © 2019 Zhong-Yu Liu et al. This is an open access article distributed under the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The following publication Zhong-Yu Liu, Man-Ting Au, Tian-Wei He, et al., “Less Vertebral Bone Mass after Treatment with Macitentan in Mice: A Pilot Study,” BioMed Research International, vol. 2019, Article ID 2075968, 6 pages, 2019 is available at
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