| Autor: |
Dwivedi, Garima, Flaman, Lisa, Alaybeyoglu, Begum, Frank, Eliot H., Black, Rebecca M., Fite, Jordan, Scherzer, Chris, Barton, Ken, Luyster, Elizabeth, Thomas, Nathan, Boland, Eugene, Krishnan, Yamini, Han-Hwa Hung, Chubinskaya, Susan, Trippel, Stephen B., Geishecker, Emily, Rosen, Vicki, Önnerfjord, Patrik, Cirit, Murat, Grodzinsky, Alan J. |
| Předmět: |
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| Zdroj: |
Frontiers in Space Technologies; 2024, p1-18, 18p |
| Abstrakt: |
Post-traumatic Osteoarthritis (PTOA) results from traumatic joint injuries (such as an ACL rupture). Mechanical impact and an immediate synovial inflammatory response can result in joint tissue degradation and longer-term progression to PTOA. Astronauts are susceptible to increased exercise-related joint injuries leading to altered musculoskeletal physiology, further escalated due to microgravity and increased exposure to ionizing radiation. We applied a human Cartilage-Bone-Synovium (CBS) coculture model to test the potential of low-dose dexamethasone (Dex) and IGF-1 in ameliorating PTOA-like degeneration on Earth and the International Space Station-National Laboratory (ISS-NL, ISS for short). CBS cocultures were established using osteochondral plugs (CB) subjected to compressive impact injury (INJ) followed by coculture with synovium (S) explants. Study groups consisted of control (CB); disease [CBS + INJ]; treatment [CBS + INJ + Dex + IGF-1]; and drugsafety [CB + Dex + IGF-1]. Outcome measures included cell viability, altered matrix glycosaminoglycans (GAG) and collagens, multiplex-ELISA quantification of released cytokines, histopathology, and metabolomic and proteomic analyses of spent media. A 21-day study on ISS-NL explored PTOA-like pathogenesis and treatment in microgravity. Tissue cards for study groups were cultured in custombuilt culture chambers within multi-use variable-g platforms (MVPs). A marked upregulation in the release of inflammatory cytokines and tissue-GAG loss was observed in CBS + INJ groups in space and ground controls utilizing tissues from the same donors, similar to that reported in a previous multi-donor study on Earth; these changes were partly ameliorated by Dex + IGF-1, but with donor variability. Metabolomic and proteomic analyses revealed an array of distinct differences between metabolites/proteins released to the medium in Space versus on Earth. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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