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

Autor: Sawamura K; Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, 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., Matsushita M; Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8550, Japan. matsushita.masaki.a7@f.mail.nagoya-u.ac.jp., Esaki R; Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8550, Japan., Mishima K; Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8550, Japan., Kamiya Y; Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8550, Japan., Ohno K; Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.; Graduate School of Nutritional Sciences, Nagoya University of Arts and Sciences, Nisshin, Aichi, 470-0196, Japan., Kitoh H; Department of Orthopaedic Surgery, Aichi Children's Health and Medical Center, Obu, Aichi, 474-8017, Japan.; Department of Comprehensive Pediatric Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan., Imagama S; Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya, Aichi, 466-8550, Japan.
Jazyk: angličtina
Zdroj: Journal of bone and mineral metabolism [J Bone Miner Metab] 2024 Nov 08. Date of Electronic Publication: 2024 Nov 08.
DOI: 10.1007/s00774-024-01563-x
Abstrakt: 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.
(© 2024. The Japanese Society Bone and Mineral Research.)
Databáze: MEDLINE
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