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Effect of Sclerostin Inactivation in a Mouse Model of Severe Osteogenesis Imperfecta

Marulanda, Juliana, Tauer, Josephine, Boraschi-Diaz, Iris, Bardai, Ghalib and Rauch, Frank (2023) Effect of Sclerostin Inactivation in a Mouse Model of Severe Osteogenesis Imperfecta. Scientific reports.

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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 Col1a1Jrt/+ mice, a model of severe OI, anti-sclerostin antibodies had a minimal skeletal effect. In the present study, we assessed the effect of genetic inactivation of sclerostin in the Col1a1Jrt/+ mouse. We crossed Col1a1Jrt/+ mice with Sost knockout mice to generate Sost-deficient Col1a1Jrt/+ mice and assessed differences between Col1a1Jrt/+ mice with homozygous Sost deficiency and Col1a1Jrt/+ mice with heterozygous Sost deficiency. We found that Col1a1Jrt/+ 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 Col1a1Jrt/+ 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.

Item Type: Article
Keywords: Bone mass, Collagen, Osteogenesis Imperfecta, Rare bone disease, Sclerostin
Date Deposited: 06 May 2023 00:46
Last Modified: 06 May 2023 00:46