Meclozine ameliorates bone mineralization and growth plate structure in a mouse model of X‑linked hypophosphatemia

Kamiya,Yasunari; Matsushita,Masaki; Mishima,Kenichi; Ohkawara,Bisei; Michigami,Toshimi; Imagama,Shiro; Ohno,Kinji; Kitoh,Hiroshi

doi:10.3892/etm.2022.11738

Meclozine ameliorates bone mineralization and growth plate structure in a mouse model of X‑linked hypophosphatemia

Authors:
- Yasunari Kamiya
- Masaki Matsushita
- Kenichi Mishima
- Bisei Ohkawara
- Toshimi Michigami
- Shiro Imagama
- Kinji Ohno
- Hiroshi Kitoh
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Affiliations: Department of Orthopaedic Surgery, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan, Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan, Department of Bone and Mineral Research, Research Institute, Osaka Women's and Children's Hospital, Osaka Prefectural Hospital Organization, Izumi, Osaka, 594‑1101, Japan, Department of Orthopaedic Surgery, Aichi Children's Health and Medical Center, Obu, Aichi 474‑8710, Japan
Published online on: November 30, 2022 https://doi.org/10.3892/etm.2022.11738
Article Number: 39
Copyright: © Kamiya et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

X‑linked hypophosphatemic rickets (XLH) is characterized by hypo‑mineralization of the bone due to hypophosphatemia. XLH is caused by abnormally high levels of fibroblast growth factor 23, which trigger renal phosphate wasting. Activated fibroblast growth factor receptor 3 (FGFR3) signaling is considered to be involved in XLH pathology. Our previous study revealed that meclozine attenuated FGFR3 signaling and promoted longitudinal bone growth in an achondroplasia mouse model. The present study aimed to examine whether meclozine affected the bone phenotype in a mouse model of XLH [X‑linked hypophosphatemic (Hyp) mice]. Meclozine was administered orally to 7‑day‑old Hyp mice for 10 days, after which the mice were subjected to blood sampling and histological analyses of the first coccygeal vertebra, femur and tibia. Villanueva Goldner staining was used to assess bone mineralization, hematoxylin and eosin staining was used to determine the growth plate structure and tartrate‑resistant acid phosphatase staining was used to measure osteoclast activity. The osteoid volume/bone volume of cortical bone was lower in meclozine‑treated Hyp mice compared with untreated Hyp mice. Meclozine treatment improved the abnormally thick hypertrophic zone of the growth plate and ameliorated the downregulation of osteoclast surface/bone surface in Hyp mice. However, meclozine had only a marginal effect on mineralization in the trabecular bone and on calcium and phosphate plasma levels. A 10‑day‑tratment with meclozine partially ameliorated bone mineralization in Hyp mice; hence, meclozine could alleviate XLH symptoms.

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