Imperfect osteogenesis (OI) is the most common genetic form of brittle bone disease and causes defects in both bone and connective tissue. Patients with OI may have significant mobility problems due to joint dysfunction due in part to tendinopathy. In a new study published in the journal Proceedings of the National Academy of Sciences, researchers at Baylor College of Medicine identify a protein signaling mechanism that drives this dysfunction and find that inhibiting this signaling pathway can prevent the onset of tendinopathy problems in mouse models.
The researchers studied mouse models of OI in which the Fkpb10 gene was removed in tendons and ligaments. Mice developed contractures, a condition in which the tendons harden, causing joint stiffness and limited movement. As a result of the deletion of the Fkpb10 gene, the researchers also observed inflammation in the joints and localized formation of pieces of cartilage in the tendon, both symptoms of chronic tendinopathy. These symptoms coincided with the increased expression of a gene that affects cell differentiation.
“We discovered an important signaling protein called Hedgehog, which is key to controlling the formation of cartilage, which had been activated in the joints,” said Dr. Brendan Lee, corresponding author of the study and chair of Molecular and Human endowed with Robert and Janice McNair. Genetics and Professor and Professor in the Department of Molecular and Human Genetics at Baylor.
The team, led by Lee and first author and postdoctoral partner of the Lee Lab, Dr. Joohyun Lim, wanted to see if genetic and pharmacological inhibition of the hedgehog signaling pathway could prevent the onset of tendinopathy symptoms.
“By giving an FDA-approved hedgehog signaling inhibitor, we delayed tendon contracture and degeneration and normalized joint function,” said Lee, director of the Baylor Center for Skeletal Medicine and Biology and co-director of the Rolanette and Berdon Bone Disease Program. of Texas. “We believe this could be a model for the treatment of tendinopathy, not only in patients with OI, but perhaps also in the patient. general population. “
In the future, researchers will also work to determine whether targeting inflammatory pathways, as well as hedgehog signaling, can prevent further tendinopathy.
Joohyun Lim et al., “Localized chondrooxification underlies joint dysfunction and motor deficits in the Fkbp10 mouse model of imperfect osteogenesis.” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.2100690118
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Citation: Understanding the Cause of Joint and Tendon Dysfunction in Imperfect Osteogenesis (2021, June 14) Retrieved June 14, 2021 from https://medicalxpress.com/news/2021-06-joint-tendon-dysfunction- osteogenesis-imperfecta.html
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