Spaceflight and hind limb unloading induces an arthritic phenotype in knee articular cartilage and menisci of rodents
Abstract Reduced knee weight-bearing from prescription or sedentary lifestyles are associated with cartilage degradation; effects on the meniscus are unclear. Rodents exposed to spaceflight or hind limb unloading (HLU) represent unique opportunities to evaluate this question. This study evaluated ar...
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Nature Portfolio
2021-05-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-021-90010-2 |
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author | Andy T. Kwok Nequesha S. Mohamed Johannes F. Plate Raghunatha R. Yammani Samuel Rosas Ted A. Bateman Eric Livingston Joseph E. Moore Bethany A. Kerr Jingyun Lee Cristina M. Furdui Li Tan Mary L. Bouxsein Virginia L. Ferguson Louis S. Stodieck David C. Zawieja Michael D. Delp Xiao W. Mao Jeffrey S. Willey |
author_facet | Andy T. Kwok Nequesha S. Mohamed Johannes F. Plate Raghunatha R. Yammani Samuel Rosas Ted A. Bateman Eric Livingston Joseph E. Moore Bethany A. Kerr Jingyun Lee Cristina M. Furdui Li Tan Mary L. Bouxsein Virginia L. Ferguson Louis S. Stodieck David C. Zawieja Michael D. Delp Xiao W. Mao Jeffrey S. Willey |
author_sort | Andy T. Kwok |
collection | DOAJ |
description | Abstract Reduced knee weight-bearing from prescription or sedentary lifestyles are associated with cartilage degradation; effects on the meniscus are unclear. Rodents exposed to spaceflight or hind limb unloading (HLU) represent unique opportunities to evaluate this question. This study evaluated arthritic changes in the medial knee compartment that bears the highest loads across the knee after actual and simulated spaceflight, and recovery with subsequent full weight-bearing. Cartilage and meniscal degradation in mice were measured via microCT, histology, and proteomics and/or biochemically after: (1) ~ 35 days on the International Space Station (ISS); (2) 13-days aboard the Space Shuttle Atlantis; or (3) 30 days of HLU, followed by a 49-day weight-bearing readaptation with/without exercise. Cartilage degradation post-ISS and HLU occurred at similar spatial locations, the tibial-femoral cartilage-cartilage contact point, with meniscal volume decline. Cartilage and meniscal glycosaminoglycan content were decreased in unloaded mice, with elevated catabolic enzymes (e.g., matrix metalloproteinases), and elevated oxidative stress and catabolic molecular pathway responses in menisci. After the 13-day Shuttle flight, meniscal degradation was observed. During readaptation, recovery of cartilage volume and thickness occurred with exercise. Reduced weight-bearing from either spaceflight or HLU induced an arthritic phenotype in cartilage and menisci, and exercise promoted recovery. |
first_indexed | 2024-12-13T17:06:01Z |
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id | doaj.art-e20ccc74580a4e1287b71ce54f1f7858 |
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issn | 2045-2322 |
language | English |
last_indexed | 2024-12-13T17:06:01Z |
publishDate | 2021-05-01 |
publisher | Nature Portfolio |
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series | Scientific Reports |
spelling | doaj.art-e20ccc74580a4e1287b71ce54f1f78582022-12-21T23:37:41ZengNature PortfolioScientific Reports2045-23222021-05-0111111710.1038/s41598-021-90010-2Spaceflight and hind limb unloading induces an arthritic phenotype in knee articular cartilage and menisci of rodentsAndy T. Kwok0Nequesha S. Mohamed1Johannes F. Plate2Raghunatha R. Yammani3Samuel Rosas4Ted A. Bateman5Eric Livingston6Joseph E. Moore7Bethany A. Kerr8Jingyun Lee9Cristina M. Furdui10Li Tan11Mary L. Bouxsein12Virginia L. Ferguson13Louis S. Stodieck14David C. Zawieja15Michael D. Delp16Xiao W. Mao17Jeffrey S. Willey18Department of Radiation Oncology, Wake Forest School of MedicineDepartment of Orthopaedic Surgery, Wake Forest School of MedicineDepartment of Orthopaedic Surgery, Wake Forest School of MedicineDepartment of Orthopaedic Surgery, Wake Forest School of MedicineDepartment of Orthopaedic Surgery, Wake Forest School of MedicineDepartment of Biomedical Engineering, University of North CarolinaDepartment of Biomedical Engineering, University of North CarolinaDepartment of Radiation Oncology, Wake Forest School of MedicineDepartment of Orthopaedic Surgery, Wake Forest School of MedicineDepartment of Internal Medicine, Section of Molecular Medicine, Wake Forest School of MedicineDepartment of Internal Medicine, Section of Molecular Medicine, Wake Forest School of MedicineDepartment of Internal Medicine, Section of Molecular Medicine, Wake Forest School of MedicineDepartment of Orthopedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Mechanical Engineering, University of Colorado At BoulderBioServe Space Technologies, Aerospace Engineering Sciences, University of Colorado At BoulderDepartment of Medical Physiology, Texas A&M University Medical SchoolDepartment of Nutrition, Food and Exercise Sciences, Florida State UniversityDivision of Biomedical Engineering Sciences (BMES), Department of Basic Sciences, Loma Linda UniversityDepartment of Radiation Oncology, Wake Forest School of MedicineAbstract Reduced knee weight-bearing from prescription or sedentary lifestyles are associated with cartilage degradation; effects on the meniscus are unclear. Rodents exposed to spaceflight or hind limb unloading (HLU) represent unique opportunities to evaluate this question. This study evaluated arthritic changes in the medial knee compartment that bears the highest loads across the knee after actual and simulated spaceflight, and recovery with subsequent full weight-bearing. Cartilage and meniscal degradation in mice were measured via microCT, histology, and proteomics and/or biochemically after: (1) ~ 35 days on the International Space Station (ISS); (2) 13-days aboard the Space Shuttle Atlantis; or (3) 30 days of HLU, followed by a 49-day weight-bearing readaptation with/without exercise. Cartilage degradation post-ISS and HLU occurred at similar spatial locations, the tibial-femoral cartilage-cartilage contact point, with meniscal volume decline. Cartilage and meniscal glycosaminoglycan content were decreased in unloaded mice, with elevated catabolic enzymes (e.g., matrix metalloproteinases), and elevated oxidative stress and catabolic molecular pathway responses in menisci. After the 13-day Shuttle flight, meniscal degradation was observed. During readaptation, recovery of cartilage volume and thickness occurred with exercise. Reduced weight-bearing from either spaceflight or HLU induced an arthritic phenotype in cartilage and menisci, and exercise promoted recovery.https://doi.org/10.1038/s41598-021-90010-2 |
spellingShingle | Andy T. Kwok Nequesha S. Mohamed Johannes F. Plate Raghunatha R. Yammani Samuel Rosas Ted A. Bateman Eric Livingston Joseph E. Moore Bethany A. Kerr Jingyun Lee Cristina M. Furdui Li Tan Mary L. Bouxsein Virginia L. Ferguson Louis S. Stodieck David C. Zawieja Michael D. Delp Xiao W. Mao Jeffrey S. Willey Spaceflight and hind limb unloading induces an arthritic phenotype in knee articular cartilage and menisci of rodents Scientific Reports |
title | Spaceflight and hind limb unloading induces an arthritic phenotype in knee articular cartilage and menisci of rodents |
title_full | Spaceflight and hind limb unloading induces an arthritic phenotype in knee articular cartilage and menisci of rodents |
title_fullStr | Spaceflight and hind limb unloading induces an arthritic phenotype in knee articular cartilage and menisci of rodents |
title_full_unstemmed | Spaceflight and hind limb unloading induces an arthritic phenotype in knee articular cartilage and menisci of rodents |
title_short | Spaceflight and hind limb unloading induces an arthritic phenotype in knee articular cartilage and menisci of rodents |
title_sort | spaceflight and hind limb unloading induces an arthritic phenotype in knee articular cartilage and menisci of rodents |
url | https://doi.org/10.1038/s41598-021-90010-2 |
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