A Systemic and Local Comparison of Senescence in an Acute Anterior Cruciate Ligament Injury—A Pilot Case Series
Background: Senescence, a characteristic of cellular aging and inflammation, has been linked to the acceleration of osteoarthritis. The purpose of this study is to prospectively identify, measure, and compare senescent profiles in synovial fluid and peripheral blood in patients with an acute knee in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/13/7/1567 |
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| author | Robert A. Waltz Kaitlyn E. Whitney Victoria R. Duke Heidi Kloser Charles Huard Matthew T. Provencher Marc J. Philippon Chelsea Bahney Jonathan A. Godin Johnny Huard |
| author_facet | Robert A. Waltz Kaitlyn E. Whitney Victoria R. Duke Heidi Kloser Charles Huard Matthew T. Provencher Marc J. Philippon Chelsea Bahney Jonathan A. Godin Johnny Huard |
| author_sort | Robert A. Waltz |
| collection | DOAJ |
| description | Background: Senescence, a characteristic of cellular aging and inflammation, has been linked to the acceleration of osteoarthritis. The purpose of this study is to prospectively identify, measure, and compare senescent profiles in synovial fluid and peripheral blood in patients with an acute knee injury within 48 h. Methods: Seven subjects, aged 18–60 years, with an acute ACL tear with effusion were prospectively enrolled. Synovial fluid and peripheral blood samples were collected and analyzed by flow cytometry, using senescent markers C12FDG and CD87. The senescent versus pro-regenerative phenotype was probed at a gene and protein level using qRT-PCR and multiplex immunoassays. Results: C<sub>12</sub>FDG and CD87 positive senescent cells were detected in the synovial fluid and peripheral blood of all patients. Pro-inflammatory <i>IL-1β</i> gene expression measured in synovial fluid was significantly higher (<i>p</i> = 0.0156) than systemic/blood expression. Senescent-associated factor MMP-3 and regenerative factor TIMP-2 were significantly higher in synovial fluid compared to blood serum. Senescent-associated factor MMP-9 and regenerative factor TGFβ-2 were significantly elevated in serum compared to synovial fluid. Correlation analysis revealed that C12FDG<sup>++</sup>/CD87<sup>++</sup> senescent cells in synovial fluid positively correlated with age-related growth-regulated-oncogene (ρ = 1.00, <i>p</i> < 0.001), IFNγ (ρ = 1.00, <i>p</i> < 0.001), IL-8 (ρ = 0.90, <i>p</i> = 0.0374), and gene marker p16 (ρ = 0.83, <i>p</i> = 0.0416). Conclusions: There is an abundance of senescent cells locally and systemically after an acute ACL tear without a significant difference between those present in peripheral blood compared to synovial fluid. This preliminary data may have a role in identifying strategies to modify the acute environment within the synovial fluid, either at the time of acute ligament injury or reconstruction surgery. |
| first_indexed | 2024-03-11T00:53:34Z |
| format | Article |
| id | doaj.art-2b44ae7ba165455c83ef2d05991a1427 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-11T00:53:34Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-2b44ae7ba165455c83ef2d05991a14272023-11-18T20:10:20ZengMDPI AGLife2075-17292023-07-01137156710.3390/life13071567A Systemic and Local Comparison of Senescence in an Acute Anterior Cruciate Ligament Injury—A Pilot Case SeriesRobert A. Waltz0Kaitlyn E. Whitney1Victoria R. Duke2Heidi Kloser3Charles Huard4Matthew T. Provencher5Marc J. Philippon6Chelsea Bahney7Jonathan A. Godin8Johnny Huard9Naval Health Clinic Annapolis, U.S. Naval Academy, Annapolis, MD 21402, USALinda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USALinda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USALinda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USALinda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USALinda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USALinda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USALinda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USALinda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USALinda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USABackground: Senescence, a characteristic of cellular aging and inflammation, has been linked to the acceleration of osteoarthritis. The purpose of this study is to prospectively identify, measure, and compare senescent profiles in synovial fluid and peripheral blood in patients with an acute knee injury within 48 h. Methods: Seven subjects, aged 18–60 years, with an acute ACL tear with effusion were prospectively enrolled. Synovial fluid and peripheral blood samples were collected and analyzed by flow cytometry, using senescent markers C12FDG and CD87. The senescent versus pro-regenerative phenotype was probed at a gene and protein level using qRT-PCR and multiplex immunoassays. Results: C<sub>12</sub>FDG and CD87 positive senescent cells were detected in the synovial fluid and peripheral blood of all patients. Pro-inflammatory <i>IL-1β</i> gene expression measured in synovial fluid was significantly higher (<i>p</i> = 0.0156) than systemic/blood expression. Senescent-associated factor MMP-3 and regenerative factor TIMP-2 were significantly higher in synovial fluid compared to blood serum. Senescent-associated factor MMP-9 and regenerative factor TGFβ-2 were significantly elevated in serum compared to synovial fluid. Correlation analysis revealed that C12FDG<sup>++</sup>/CD87<sup>++</sup> senescent cells in synovial fluid positively correlated with age-related growth-regulated-oncogene (ρ = 1.00, <i>p</i> < 0.001), IFNγ (ρ = 1.00, <i>p</i> < 0.001), IL-8 (ρ = 0.90, <i>p</i> = 0.0374), and gene marker p16 (ρ = 0.83, <i>p</i> = 0.0416). Conclusions: There is an abundance of senescent cells locally and systemically after an acute ACL tear without a significant difference between those present in peripheral blood compared to synovial fluid. This preliminary data may have a role in identifying strategies to modify the acute environment within the synovial fluid, either at the time of acute ligament injury or reconstruction surgery.https://www.mdpi.com/2075-1729/13/7/1567synovial fluidperipheral blood mononuclear cells (PBMCs)senescencesenescence associated secretory phenotype (SASP)post-traumatic arthritis (PTOA)ACL |
| spellingShingle | Robert A. Waltz Kaitlyn E. Whitney Victoria R. Duke Heidi Kloser Charles Huard Matthew T. Provencher Marc J. Philippon Chelsea Bahney Jonathan A. Godin Johnny Huard A Systemic and Local Comparison of Senescence in an Acute Anterior Cruciate Ligament Injury—A Pilot Case Series Life synovial fluid peripheral blood mononuclear cells (PBMCs) senescence senescence associated secretory phenotype (SASP) post-traumatic arthritis (PTOA) ACL |
| title | A Systemic and Local Comparison of Senescence in an Acute Anterior Cruciate Ligament Injury—A Pilot Case Series |
| title_full | A Systemic and Local Comparison of Senescence in an Acute Anterior Cruciate Ligament Injury—A Pilot Case Series |
| title_fullStr | A Systemic and Local Comparison of Senescence in an Acute Anterior Cruciate Ligament Injury—A Pilot Case Series |
| title_full_unstemmed | A Systemic and Local Comparison of Senescence in an Acute Anterior Cruciate Ligament Injury—A Pilot Case Series |
| title_short | A Systemic and Local Comparison of Senescence in an Acute Anterior Cruciate Ligament Injury—A Pilot Case Series |
| title_sort | systemic and local comparison of senescence in an acute anterior cruciate ligament injury a pilot case series |
| topic | synovial fluid peripheral blood mononuclear cells (PBMCs) senescence senescence associated secretory phenotype (SASP) post-traumatic arthritis (PTOA) ACL |
| url | https://www.mdpi.com/2075-1729/13/7/1567 |
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