Lose‐Dose Administration of Dexamethasone is Beneficial in Preventing Secondary Tendon Damage in a Stress‐Deprived Joint Injury Explant Model
© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. Secondary joint damage is the process by which a single injury can lead to detrimental changes in adjacent tissue structures, typically through the spread of inflammatory responses. We recently developed an in vitro model of s...
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| Format: | Article |
| Language: | English |
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Wiley
2021
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| Online Access: | https://hdl.handle.net/1721.1/133528 |
| _version_ | 1811071362593193984 |
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| author | Connizzo, Brianne K Grodzinsky, Alan J |
| author_facet | Connizzo, Brianne K Grodzinsky, Alan J |
| author_sort | Connizzo, Brianne K |
| collection | MIT |
| description | © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. Secondary joint damage is the process by which a single injury can lead to detrimental changes in adjacent tissue structures, typically through the spread of inflammatory responses. We recently developed an in vitro model of secondary joint damage using a murine rotator cuff explant system, in which injuries to muscle and bone cause massive cell death in otherwise uninjured tendon. The purpose of the present study was to test the ability cytokine-targeted and broad-spectrum therapeutics to prevent cell death and tissue degeneration associated with secondary joint damage. We treated injured bone-tendon-muscle explants with either interleukin-1 receptor antagonist, etanercept, or dexamethasone (DEX) for up to 7 days in culture. Only the low-dose DEX treatment was able to prevent cell death and tissue degeneration. We then identified a critical window between 24 and 72 h following injury for maximal benefit of DEX treatment through timed administration experiments. Finally, we performed two tendon-only explant studies to identify mechanistic effects on tendon health. Interestingly, DEX did not prevent cell death and degeneration in a model of cytokine-induced damage, suggesting other targets of DEX activity. Future studies will aim to identify factors in joint inflammation that may be targeted by DEX treatment, as well as to investigate novel delivery strategies. Statement of clinical significance: Overall, this work demonstrates beneficial effects of DEX administration on preventing tenocyte death and extracellular matrix degeneration in an explant model of secondary joint damage, supporting the clinical use of low-dose glucocorticoids for short-term treatment of joint inflammation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:139–149, 2020. |
| first_indexed | 2024-09-23T08:50:01Z |
| format | Article |
| id | mit-1721.1/133528 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:50:01Z |
| publishDate | 2021 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1335282021-10-28T04:53:01Z Lose‐Dose Administration of Dexamethasone is Beneficial in Preventing Secondary Tendon Damage in a Stress‐Deprived Joint Injury Explant Model Connizzo, Brianne K Grodzinsky, Alan J © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. Secondary joint damage is the process by which a single injury can lead to detrimental changes in adjacent tissue structures, typically through the spread of inflammatory responses. We recently developed an in vitro model of secondary joint damage using a murine rotator cuff explant system, in which injuries to muscle and bone cause massive cell death in otherwise uninjured tendon. The purpose of the present study was to test the ability cytokine-targeted and broad-spectrum therapeutics to prevent cell death and tissue degeneration associated with secondary joint damage. We treated injured bone-tendon-muscle explants with either interleukin-1 receptor antagonist, etanercept, or dexamethasone (DEX) for up to 7 days in culture. Only the low-dose DEX treatment was able to prevent cell death and tissue degeneration. We then identified a critical window between 24 and 72 h following injury for maximal benefit of DEX treatment through timed administration experiments. Finally, we performed two tendon-only explant studies to identify mechanistic effects on tendon health. Interestingly, DEX did not prevent cell death and degeneration in a model of cytokine-induced damage, suggesting other targets of DEX activity. Future studies will aim to identify factors in joint inflammation that may be targeted by DEX treatment, as well as to investigate novel delivery strategies. Statement of clinical significance: Overall, this work demonstrates beneficial effects of DEX administration on preventing tenocyte death and extracellular matrix degeneration in an explant model of secondary joint damage, supporting the clinical use of low-dose glucocorticoids for short-term treatment of joint inflammation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:139–149, 2020. 2021-10-27T19:53:21Z 2021-10-27T19:53:21Z 2020 2021-09-03T13:05:35Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133528 en 10.1002/JOR.24451 Journal of Orthopaedic Research Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley PMC |
| spellingShingle | Connizzo, Brianne K Grodzinsky, Alan J Lose‐Dose Administration of Dexamethasone is Beneficial in Preventing Secondary Tendon Damage in a Stress‐Deprived Joint Injury Explant Model |
| title | Lose‐Dose Administration of Dexamethasone is Beneficial in Preventing Secondary Tendon Damage in a Stress‐Deprived Joint Injury Explant Model |
| title_full | Lose‐Dose Administration of Dexamethasone is Beneficial in Preventing Secondary Tendon Damage in a Stress‐Deprived Joint Injury Explant Model |
| title_fullStr | Lose‐Dose Administration of Dexamethasone is Beneficial in Preventing Secondary Tendon Damage in a Stress‐Deprived Joint Injury Explant Model |
| title_full_unstemmed | Lose‐Dose Administration of Dexamethasone is Beneficial in Preventing Secondary Tendon Damage in a Stress‐Deprived Joint Injury Explant Model |
| title_short | Lose‐Dose Administration of Dexamethasone is Beneficial in Preventing Secondary Tendon Damage in a Stress‐Deprived Joint Injury Explant Model |
| title_sort | lose dose administration of dexamethasone is beneficial in preventing secondary tendon damage in a stress deprived joint injury explant model |
| url | https://hdl.handle.net/1721.1/133528 |
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