Meclozine and growth hormone ameliorate bone length and quality in experimental models of achondroplasia.

IF 2.4 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM Journal of Bone and Mineral Metabolism Pub Date : 2024-11-08 DOI:10.1007/s00774-024-01563-x
Kenta Sawamura, Masaki Matsushita, Ryusaku Esaki, Kenichi Mishima, Yasunari Kamiya, Kinji Ohno, Hiroshi Kitoh, Shiro Imagama
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Abstract

Introduction: Achondroplasia (ACH) is a common skeletal dysplasia associated with short-limbed short stature caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Meclozine was found to inhibit FGFR3 signaling using a drug repositioning strategy. In some countries, growth hormone (GH) has been employed to ameliorate short stature in children with ACH. This study aims to investigate the effects of meclozine and GH on bone growth and quality using an experimental model of ACH.

Materials and methods: Meclozine (2 mg/kg/day) and/or GH (0.35 mg/kg/day) were administered to a mouse model of ACH from the age of 7 to 56 days. Body length and body weight of each mouse were measured during these treatments. At the end of treatments, these mice were subjected to micro-computed tomography scans to measure the lengths of long bones and bone mineral density (BMD). The width of the growth plate was quantified by histological analysis.

Results: The body and bone length of transgenic mice significantly increased after treatment with meclozine and GH, although there was no additive effect of the combination therapy on promoting bone growth. In contrast, BMD was additively increased by the combination therapy. The width of the growth plate in transgenic mice was significantly increased by both treatments, although the hypertrophic zone was enlarged by meclozine but not by GH.

Conclusion: Meclozine or GH may be an option for treating children with ACH to ameliorate bone length and quality, but the additive effect would be limited.

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美克洛嗪和生长激素可改善软骨发育不全实验模型的骨长度和骨质量。
导言:软骨发育不全症(ACH)是一种常见的骨骼发育不良症,由于成纤维细胞生长因子受体 3(FGFR3)基因的功能增益突变而导致短肢矮身材。研究发现,美克洛嗪可通过药物重新定位策略抑制 FGFR3 信号传导。在一些国家,生长激素(GH)被用于改善ACH患儿的身材矮小。本研究旨在通过ACH实验模型,研究美克洛嗪和GH对骨骼生长和质量的影响:给7至56天大的ACH小鼠模型注射美克洛嗪(2毫克/千克/天)和/或GH(0.35毫克/千克/天)。在治疗期间测量每只小鼠的体长和体重。治疗结束后,对这些小鼠进行微型计算机断层扫描,以测量长骨的长度和骨矿物质密度(BMD)。生长板的宽度通过组织学分析进行量化:结果:使用美克洛嗪和 GH 治疗后,转基因小鼠的体长和骨长明显增加,但联合疗法对促进骨生长没有叠加效应。与此相反,联合疗法可增加骨密度。两种疗法都能显著增加转基因小鼠生长板的宽度,但美克洛嗪能扩大肥厚区,而 GH 却不能:结论:美克洛嗪或 GH 可用于治疗 ACH 儿童,以改善骨长度和骨质量,但其叠加效应有限。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Bone and Mineral Metabolism
Journal of Bone and Mineral Metabolism 医学-内分泌学与代谢
CiteScore
6.30
自引率
3.00%
发文量
89
审稿时长
6-12 weeks
期刊介绍: The Journal of Bone and Mineral Metabolism (JBMM) provides an international forum for researchers and clinicians to present and discuss topics relevant to bone, teeth, and mineral metabolism, as well as joint and musculoskeletal disorders. The journal welcomes the submission of manuscripts from any country. Membership in the society is not a prerequisite for submission. Acceptance is based on the originality, significance, and validity of the material presented. The journal is aimed at researchers and clinicians dedicated to improvements in research, development, and patient-care in the fields of bone and mineral metabolism.
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