Impaired bone strength and bone microstructure in a novel early-onset osteoporotic rat model with a clinically relevant PLS3 mutation
| Title: | Impaired bone strength and bone microstructure in a novel early-onset osteoporotic rat model with a clinically relevant PLS3 mutation |
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| Authors: | Jing Hu, Bingna Zhou, Xiaoyun Lin, Qian Zhang, Feifei Guan, Lei Sun, Jiayi Liu, Ou Wang, Yan Jiang, Wei-bo Xia, Xiaoping Xing, Mei Li |
| Source: | eLife, Vol 12 (2023) |
| Publisher Information: | eLife Sciences Publications Ltd, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | a novel rat model with PLS3 mutation, early-onset osteoporosis, alendronate, teriparatide, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | 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 µg/kg/day) or teriparatide (40 µg/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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/80365; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.80365 |
| Access URL: | https://doaj.org/article/4b44a117e1c14a5eab38051ce4b1a4f9 |
| Accession Number: | edsdoj.4b44a117e1c14a5eab38051ce4b1a4f9 |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.80365 |
| Published in: | eLife |
| Language: | English |