Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 25;40(7):881-890.
doi: 10.1093/jbmr/zjaf068.

Anti-transforming growth factor-β treatment shows increased bone mass and strength in a novel mouse model for osteogenesis imperfecta type I

Ellen Busschers  1 , Yuqing Chen-Everson  1 , Mary Adeyeye  1   2 , I-Wen Song  1 , Emily Busse  1   3 , Alexis Castellon  1 , Oscar Ruiz  1 , Nicole Meyers  4 , Yangjin Bae  1 , Catherine Ambrose  4 , Brendan Lee  1
Affiliations

Anti-transforming growth factor-β treatment shows increased bone mass and strength in a novel mouse model for osteogenesis imperfecta type I

Ellen Busschers et al. J Bone Miner Res. .

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: 1D11; OI type I; collagen type I; osteogenesis imperfecta; transforming growth factor β (TGF-β).

Plain language summary

Osteogenesis imperfecta is a genetic disease associated with skeletal fragility. Here, we show that a mouse model for the most common form of osteogenesis imperfecta, type I, has a bone phenotype that recapitulates patient phenotypes. Treatment with anti-transforming growth factor -β therapy increases bone mass and strength in these mice.

PubMed Disclaimer

Conflict of interest statement

Disclosure the 1D11 and 13C4 antibodies were provided by Sanofi. Baylor College of Medicine has licensed the discovery "Treatment of Osteogenesis Imperfecta or brittle bone disease with anti-TGFb treatment" to Sanofi.

References

    1. Jovanovic M, Guterman-Ram G, Marini JC. Osteogenesis imperfecta: mechanisms and signaling pathways connecting classical and rare OI types. Endocr Rev. 2022;43(1):61-90. 10.1210/endrev/bnab017 - DOI - PMC - PubMed
    1. Rossi V, Lee B, Marom R. Osteogenesis imperfecta: advancements in genetics and treatment. Curr Opin Pediatr. 2019;31(6):708-715. 10.1097/MOP.0000000000000813 - DOI - PMC - PubMed
    1. Forlino A, Marini JC. Osteogenesis imperfecta. Lancet. 2016;387(10028):1657-1671. 10.1016/S0140-6736(15)00728-X - DOI - PMC - PubMed
    1. Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. 2004;363(9418):1377-1385. 10.1016/S0140-6736(04)16051-0 - DOI - PubMed
    1. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979;16(2):101-116. 10.1136/jmg.16.2.101 - DOI - PMC - PubMed

MeSH terms

Substances