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Prostaglandin E2 (PGE 2 ) is an FDA approved lipid signaling molecule for range of disorders. Also, it has a significant therapeutic potential for tissue repair and regeneration. However, to date there are no applications of PGE 2 specifically designed for the muscle repair and regeneration. Liposome systems offer several advantages for PGE 2 delivery, improved drug stability, reduced side effects, and tissue-specific targeting. Our hypothesis is that encapsulating PGE 2 in liposome system will significantly enhance its bioavailability and maintain an effective therapeutic level. The research was designed to optimize PGE 2 concentration in muscle cells, study its effect on cells differentiation, use the optimized PGE 2 concentration for liposome-loading and testing the delivery system in-vitro and in-vivo using muscle injury models. We further investigated the molecular mechanism and signaling pathways triggered by the intracellular elevation of PGE 2 in muscle cells. Optimization results revealed that nM concentration of PGE 2 was beneficial while μM concentrations were detrimental. All our studies reported here were conducted with 50nM PGE 2 . 50nM PGE 2 significantly enhances proliferation and myogenic differentiation as indicated by increased fusion index ( p=0.02) compared to a control. Scanning Electron Microscopy (SEM) images confirmed the lipid bi-layer formation with core-shell structure of 3μm liposomes containing PGE 2 . In-vitro studies on the C2C12 muscles cells showed that PGE 2 -liposome system significantly increased the intracellular concentration of PGE 2 compared to a PGE 2 -vehicle (DMSO) control ( p=0.019), confirming the effcacy of this delivery system. Additionally, 50nM PGE 2 significantly regulated myogenic signaling pathways and genes associated with calcium homeostasis, mitochondrial biogenesis, cellular hypertrophy, and oxidative stress. These findings support the notion that PGE 2 induces the acceleration of myogenic differentiation which is supported by our initial signaling pathway analysis. Our in-vitro muscle damage model indicated that 50nM PGE 2 can significantly attenuate the muscle damage and regenerate myotubes within 48 hours compared to 4 days in normal control. In conclusion, the findings suggest that liposome-PGE 2 delivery system can positively influence myogenic differentiation, muscle properties, and cellular signaling pathways, offering promise for improving the delivery of PGE 2 to injured skeletal muscles to assist in their regeneration process. This work was directly supported by NIH-National Institutes of Aging P01AG039355 (MB) and the George W. and Hazel M. Jay and Evanston Research Endowments (MB). Authors were supported by NIH Grants: National Institutes of Aging (NINDS) 2-R01NS105621; NIA-R01AG056504, NIA-2R01AG060341, National Institutes of Diabetes, Digestive, and Kidney Diseases Kidney (NIDDK)-1R01DK119066 to MB, and National Institutes of Neurological Disorders and Stroke (NINDS) 2-R01NS105621 to MB. Also, NIH/NIDC 1R01DE031872-01 (VV). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Yacoub et al. (Wed,) studied this question.