Language
English
Publication Date
6-25-2025
Journal
Journal of Bone and Mineral Research
DOI
10.1093/jbmr/zjaf068
PMID
40358008
PMCID
PMC12188749
PubMedCentral® Posted Date
5-13-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Anti-transforming growth factor beta (TGF-β) is a promising approach for the treatment of osteogenesis imperfecta (OI). To date, preclinical and clinical studies for the use of anti-TGF-β therapy have focused on moderate to severe OI caused by qualitative defects in collagen. However, the majority of OI patients are represented by type I OI. Mutations resulting in the haploinsufficiency of type I collagen is the cause of OI type I in the majority of patients. To study the effect of anti-TGF-β therapy in type I OI, we generated a novel mouse model for OI type I. CMV-CRE mice were crossed to mice where Col1a1 was floxed between exon 2 and 5 to create a full body heterozygous deletion of Col1a1. Haploinsufficiency of Col1a1 in the tibia was confirmed by decreased Col1a1 mRNA and protein expression. Comparable to OI patients, we observed reduced bone mass by μCT in these Col1a1+/- mice. Biomechanical measurements showed a decrease in bone strength and an increase in bone brittleness. Histomorphometric analysis showed an increase in osteoclast number and a trend towards increased osteoblast number supporting a high bone turnover phenotype, similar to OI type I patients. Upon treatment with a pan anti-TGF-β antibody, 1D11, Col1a1+/- mice showed increased bone mass and improved ultimate strength, but measures of ductility did not show improvement. Overall, our findings support expanding the study of anti-TGF-β treatment to OI caused by haploinsufficiency of type I collagen.
Keywords
Animals, Osteogenesis Imperfecta, Disease Models, Animal, Collagen Type I, Mice, Collagen Type I, alpha 1 Chain, Transforming Growth Factor beta, Bone and Bones, Osteoclasts, Bone Density, Organ Size, Haploinsufficiency, X-Ray Microtomography, Osteoblasts, Tibia, Female, osteogenesis imperfecta, transforming growth factor β (TGF-β), collagen type I, OI type I, 1D11
Published Open-Access
yes
Recommended Citation
Busschers, Ellen; Chen-Everson, Yuqing; Adeyeye, Mary; et al., "Anti-Transforming Growth Factor-β Treatment Shows Increased Bone Mass and Strength in a Novel Mouse Model for Osteogenesis Imperfecta Type I" (2025). Faculty, Staff and Students Publications. 7100.
https://digitalcommons.library.tmc.edu/baylor_docs/7100