Skeletal Effects of Bone-Targeted TGFbeta Inhibition in a Mouse Model of Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a severe progressive muscle disease that is frequently associated with secondary osteoporosis. Previous studies have shown that TGFbeta inactivating antibody improves the muscle phenotype in <i>mdx</i> mice, a model of DMD. In the present study, we as...
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MDPI AG
2021-08-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/11/8/791 |
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| author | Juliana Marulanda Iris Boraschi-Diaz Pierre Beauparlant Philippe Crine Frank Rauch |
| author_facet | Juliana Marulanda Iris Boraschi-Diaz Pierre Beauparlant Philippe Crine Frank Rauch |
| author_sort | Juliana Marulanda |
| collection | DOAJ |
| description | Duchenne muscular dystrophy (DMD) is a severe progressive muscle disease that is frequently associated with secondary osteoporosis. Previous studies have shown that TGFbeta inactivating antibody improves the muscle phenotype in <i>mdx</i> mice, a model of DMD. In the present study, we assessed the skeletal effects of treatment with a bone-targeted TGFbeta antibody (PCT-011) in <i>mdx</i> mice. Micro-computed tomography showed that 8 weeks of intraperitoneal administration of PCT-011 (10 mg per kg body mass, 3 times per week) was associated with more than twofold higher trabecular bone volume at the distal femur, which was explained by a higher trabecular number. At the femoral midshaft, PCT-011 exposure increased cortical thickness but did not significantly affect the results of three-point bending tests. Histomorphometric analyses of the lumbar vertebra 4 showed that PCT-011 treatment led to a lower bone formation rate. In conclusion, treatment with the TGFbeta antibody PCT-011 had a positive effect on bone development in <i>mdx</i> mice. Inhibiting TGFbeta activity thus appears to be a promising approach to treat bone fragility in the context of DMD. |
| first_indexed | 2024-03-10T08:39:46Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T08:39:46Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-24208329d2b14873ae244265c532653f2023-11-22T08:22:57ZengMDPI AGLife2075-17292021-08-0111879110.3390/life11080791Skeletal Effects of Bone-Targeted TGFbeta Inhibition in a Mouse Model of Duchenne Muscular DystrophyJuliana Marulanda0Iris Boraschi-Diaz1Pierre Beauparlant2Philippe Crine3Frank Rauch4Shriners Hospital for Children-Canada, Montreal, QC H4A 0A9, CanadaShriners Hospital for Children-Canada, Montreal, QC H4A 0A9, CanadaPreciThera Inc., Montreal, QC H3A 2R7, CanadaPreciThera Inc., Montreal, QC H3A 2R7, CanadaShriners Hospital for Children-Canada, Montreal, QC H4A 0A9, CanadaDuchenne muscular dystrophy (DMD) is a severe progressive muscle disease that is frequently associated with secondary osteoporosis. Previous studies have shown that TGFbeta inactivating antibody improves the muscle phenotype in <i>mdx</i> mice, a model of DMD. In the present study, we assessed the skeletal effects of treatment with a bone-targeted TGFbeta antibody (PCT-011) in <i>mdx</i> mice. Micro-computed tomography showed that 8 weeks of intraperitoneal administration of PCT-011 (10 mg per kg body mass, 3 times per week) was associated with more than twofold higher trabecular bone volume at the distal femur, which was explained by a higher trabecular number. At the femoral midshaft, PCT-011 exposure increased cortical thickness but did not significantly affect the results of three-point bending tests. Histomorphometric analyses of the lumbar vertebra 4 showed that PCT-011 treatment led to a lower bone formation rate. In conclusion, treatment with the TGFbeta antibody PCT-011 had a positive effect on bone development in <i>mdx</i> mice. Inhibiting TGFbeta activity thus appears to be a promising approach to treat bone fragility in the context of DMD.https://www.mdpi.com/2075-1729/11/8/791bone remodelingDuchenne muscular dystrophyfracturestransforming growth factor beta |
| spellingShingle | Juliana Marulanda Iris Boraschi-Diaz Pierre Beauparlant Philippe Crine Frank Rauch Skeletal Effects of Bone-Targeted TGFbeta Inhibition in a Mouse Model of Duchenne Muscular Dystrophy Life bone remodeling Duchenne muscular dystrophy fractures transforming growth factor beta |
| title | Skeletal Effects of Bone-Targeted TGFbeta Inhibition in a Mouse Model of Duchenne Muscular Dystrophy |
| title_full | Skeletal Effects of Bone-Targeted TGFbeta Inhibition in a Mouse Model of Duchenne Muscular Dystrophy |
| title_fullStr | Skeletal Effects of Bone-Targeted TGFbeta Inhibition in a Mouse Model of Duchenne Muscular Dystrophy |
| title_full_unstemmed | Skeletal Effects of Bone-Targeted TGFbeta Inhibition in a Mouse Model of Duchenne Muscular Dystrophy |
| title_short | Skeletal Effects of Bone-Targeted TGFbeta Inhibition in a Mouse Model of Duchenne Muscular Dystrophy |
| title_sort | skeletal effects of bone targeted tgfbeta inhibition in a mouse model of duchenne muscular dystrophy |
| topic | bone remodeling Duchenne muscular dystrophy fractures transforming growth factor beta |
| url | https://www.mdpi.com/2075-1729/11/8/791 |
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