Impaired bone strength and bone microstructure in a novel early-onset osteoporotic rat model with a clinically relevant PLS3 mutation
- Peking Union Medical College Hospital, China
- Peking Union Medical College, China
Abstract
Plastin 3 (PLS3), a protein involved in formation of filamentous actin (F-actin) bundles, is important in human bone health. Recent studies identify PLS3 as a novel bone regulator and PLS3 mutations can lead to a rare monogenic early-onset osteoporosis. However, the mechanism of PLS3 mutation leading to osteoporosis is unknown, and its effective treatment strategies have not been established. Here we have constructed a novel rat model with clinically relevant hemizygous E10-16del mutation in PLS3 (PLS3E10-16del/0) that recapitulates the osteoporotic phenotypes with obviously thinner cortical thickness, significant decreases in yield load, maximum load, and breaking load of femora at 3, 6, 9 months old compared to wild type rats. Histomorphometric analysis indicates a significantly lower mineral apposition rate in PLS3E10-16del/0 rats. Treatment with alendronate (1.0 ug/kg per day) or teriparatide (40ug/kg five times weekly) for 8 weeks significantly improves bone mass and bone microarchitecture, and bone strength is significantly increased after teriparatide treatment (P＜0.05). Thus, our results indicate that PLS3 plays an important role in the regulation of bone microstructure and bone strength, and we provide a novel animal model for the study of X-linked early-onset osteoporosis. Alendronate and teriparatide treatment could be a potential treatment for early-onset osteoporosis induced by PLS3 mutation.
Data availability
All data analyzed during this study are included in the manuscript and supporting file. Source Data files have been provided for Figures 1-4.
Article and author information
Author details
Funding
National Key Research and Development Program of China (2018YFA0800801,2021YFC2501704)
- Mei Li
Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2021-I2M-C&T-B-007,2021-I2M-1-051)
- Mei Li
National Natural Science Foundation of China (No.81873668,82070908)
- Mei Li
Beijing Natural Science Foundation (7202153)
- Mei Li
Fundamental Research Funds for the Central Universities (3332022102)
- Jing Hu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal experiments were approved by the Institutional Animal Care and Use Committee of the Peking Union Medical College Hospital (XHDW-2021-027). Every effort was made to minimize pain and suffering by providing support when necessary and choosing ethical endpoints.
Copyright
© 2023, Hu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Impaired bone strength and bone microstructure in a novel early-onset osteoporotic rat model with a clinically relevant PLS3 mutation
eLife 12:e80365.
https://doi.org/10.7554/eLife.80365
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