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Growth Hormone (GH) is an FDA approved drug to treat certain diseases such as growth hormone deficiency (GHD). Additionally, GH secretion decreases over time, causing some older adults to consider the use of GH replacement as a means to counteract aging related conditions. However, over-production or prolonged usage of GH has been reported to have many side effects including joint degeneration and joint pain. Identifying the mechanisms by which GH causes joint cell dysfunction during aging could inform effective interventions and therapeutic strategies that reduce the incidence and impact of OA. Our preliminary studies have shown that over-expression of GH gene in mice predispose mice into progressive joint degeneration, while blocking GH action through systemic GH receptor disruption protect mice from developing OA. We showed that GH robustly altered the metabolism of cells (i.e, chondrocytes) in cartilage (Arthritis & Rheumatology, 2023). Yet, it is still unknown if blocking GH¡¯s action specifically on cartilage tissue would be protective. In this project, several genetically modified mouse models, in vivo and in vitro metabolic profiling methods will be leveraged to determine the effects of manipulating GH signaling on chondrocyte cellular metabolism. Last but not least, a unique mouse model that was used for discovery of Pegvisomant, an FDA approved drug for treating acromegaly, will be used to test if blocking GH is beneficial for joint health.

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https://ou.theopenscholar.com/zhu-shouan/
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https://www.researchgate.net/profile/Shouan-Zhu-2
https://scholar.google.com/citations?user=5DPLUl4AAAAJ

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