Suppression of Heterotopic Ossification Using a TAK1 Inhibitor – UROP Spring Symposium 2021

Suppression of Heterotopic Ossification Using a TAK1 Inhibitor

Isabelle George

Isabelle George

Research Mentor(s): Yuji Mishina, Professor
Research Mentor School/College/Department: Biological and Material Sciences, School of Dentistry
Presentation Date: Thursday, April 22, 2021
Session: Session 3 (1pm-1:50pm)
Breakout Room: Room 10
Presenter: 1

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Heterotopic ossification (or HO) is the abnormal growth of bone in soft tissues, such as muscles, tendons, and more which cause the subject to develop excruciating pain in their joints. After seeing how negatively HO affects a patient’s life, there is a clear need for prevention of the lesions to help improve the life of someone with HO. The host lab previously found that genetic or pharmacologic suppression of TGF-beta activated kinase 1 (TAK1) is efficient to mitigate HO. A next logical step of the study regarding HO is that the lowest possible dose of a TAK1 inhibitor, Takinib, with co-treatment of an anti-inflammatory drug, rapamycin, will suppress the growth of heterotopic ossification in mice. After induction of HO in our genetic mouse model for HO, a suboptimal dose of Takinib was orally administered with a range of rapamycin. Tissues with resulted HO were scanned by the micro-CT 500 microscopy scanner. CT scans of experimental mice with HO were investigated using a software called ITK Snap, which helps find the volume of the HO throughout the mice. The volumetric measurements revealed that combinations of suboptimal doses of Takinib and rapamycin effectively suppressed the growth of HO, or bone growth in soft tissues. Our findings suggest that co-treatment of TAK1 inhibitors with anti-inflammatory drugs, such as rapamycin, is the way to suppress the growth of heterotopic ossification with minimal side effects of each chemical. The study hopes to identify the lowest dose of the main anti-inflammatory chemical and how this dose will be effective in reducing the growth of HO. The identified chemical dose will ultimately serve as an efficient treatment for HO without adverse reactions not only in mice, but also in humans.

Authors: Isabelle George, Haichun Pan, Yuji Mishina
Research Method: Laboratory Research with Animals

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