Effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfecta
Abstract Osteogenesis imperfecta (OI) is a rare bone disease that is associated with fractures and low bone mass. Sclerostin inhibition is being evaluated as a potential approach to increase bone mass in OI. We had previously found that in Col1a1 Jrt/+ mice, a model of severe OI, treatment with an a...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-32221-3 |
| _version_ | 1797853764931026944 |
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| author | Juliana Marulanda Josephine T. Tauer Iris Boraschi-Diaz Ghalib Bardai Frank Rauch |
| author_facet | Juliana Marulanda Josephine T. Tauer Iris Boraschi-Diaz Ghalib Bardai Frank Rauch |
| author_sort | Juliana Marulanda |
| collection | DOAJ |
| description | Abstract Osteogenesis imperfecta (OI) is a rare bone disease that is associated with fractures and low bone mass. Sclerostin inhibition is being evaluated as a potential approach to increase bone mass in OI. We had previously found that in Col1a1 Jrt/+ mice, a model of severe OI, treatment with an anti-sclerostin antibody had a minor effect on the skeletal phenotype. In the present study, we assessed the effect of genetic sclerostin inactivation in the Col1a1 Jrt/+ mouse. We crossed Col1a1 Jrt/+ mice with Sost knockout mice to generate Sost-deficient Col1a1 Jrt/+ mice and assessed differences between Col1a1 Jrt/+ mice with homozygous Sost deficiency and Col1a1 Jrt/+ mice with heterozygous Sost deficiency. We found that Col1a1 Jrt/+ mice with homozygous Sost deficiency had higher body mass, femur length, trabecular bone volume, cortical thickness and periosteal diameter as well as increased biomechanical parameters of bone strength. Differences between genotypes were larger at the age of 14 weeks than at 8 weeks of age. Transcriptome analysis of RNA extracted from the tibial diaphysis revealed only 5 differentially regulated genes. Thus, genetic inactivation of Sost increased bone mass and strength in the Col1a1 Jrt/+ mouse. It appears from these observations that the degree of Sost suppression that is required for eliciting a beneficial response can vary with the genetic cause of OI. |
| first_indexed | 2024-04-09T19:56:01Z |
| format | Article |
| id | doaj.art-159067d733a54de487fe954a2d222d85 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T19:56:01Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-159067d733a54de487fe954a2d222d852023-04-03T05:27:06ZengNature PortfolioScientific Reports2045-23222023-03-011311910.1038/s41598-023-32221-3Effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfectaJuliana Marulanda0Josephine T. Tauer1Iris Boraschi-Diaz2Ghalib Bardai3Frank Rauch4Shriners Hospital for ChildrenShriners Hospital for ChildrenDepartment of Pediatrics, McGill UniversityShriners Hospital for ChildrenShriners Hospital for ChildrenAbstract Osteogenesis imperfecta (OI) is a rare bone disease that is associated with fractures and low bone mass. Sclerostin inhibition is being evaluated as a potential approach to increase bone mass in OI. We had previously found that in Col1a1 Jrt/+ mice, a model of severe OI, treatment with an anti-sclerostin antibody had a minor effect on the skeletal phenotype. In the present study, we assessed the effect of genetic sclerostin inactivation in the Col1a1 Jrt/+ mouse. We crossed Col1a1 Jrt/+ mice with Sost knockout mice to generate Sost-deficient Col1a1 Jrt/+ mice and assessed differences between Col1a1 Jrt/+ mice with homozygous Sost deficiency and Col1a1 Jrt/+ mice with heterozygous Sost deficiency. We found that Col1a1 Jrt/+ mice with homozygous Sost deficiency had higher body mass, femur length, trabecular bone volume, cortical thickness and periosteal diameter as well as increased biomechanical parameters of bone strength. Differences between genotypes were larger at the age of 14 weeks than at 8 weeks of age. Transcriptome analysis of RNA extracted from the tibial diaphysis revealed only 5 differentially regulated genes. Thus, genetic inactivation of Sost increased bone mass and strength in the Col1a1 Jrt/+ mouse. It appears from these observations that the degree of Sost suppression that is required for eliciting a beneficial response can vary with the genetic cause of OI.https://doi.org/10.1038/s41598-023-32221-3 |
| spellingShingle | Juliana Marulanda Josephine T. Tauer Iris Boraschi-Diaz Ghalib Bardai Frank Rauch Effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfecta Scientific Reports |
| title | Effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfecta |
| title_full | Effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfecta |
| title_fullStr | Effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfecta |
| title_full_unstemmed | Effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfecta |
| title_short | Effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfecta |
| title_sort | effect of sclerostin inactivation in a mouse model of severe dominant osteogenesis imperfecta |
| url | https://doi.org/10.1038/s41598-023-32221-3 |
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