Decreased SIRT1 Activity Is Involved in the Acute Injury Response of Chondrocytes to Ex Vivo Injurious Mechanical Overload
A better understanding of molecular events following cartilage injury is required to develop treatments that prevent or delay the onset of trauma-induced osteoarthritis. In this study, alterations to SIRT1 activity in bovine articular cartilage explants were evaluated in the 24 h following a mechani...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6521 |
| _version_ | 1797607715878469632 |
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| author | Sonali Karnik Hessam Noori-Dokht Taylor Williams Amin Joukar Stephen B. Trippel Uma Sankar Diane R. Wagner |
| author_facet | Sonali Karnik Hessam Noori-Dokht Taylor Williams Amin Joukar Stephen B. Trippel Uma Sankar Diane R. Wagner |
| author_sort | Sonali Karnik |
| collection | DOAJ |
| description | A better understanding of molecular events following cartilage injury is required to develop treatments that prevent or delay the onset of trauma-induced osteoarthritis. In this study, alterations to SIRT1 activity in bovine articular cartilage explants were evaluated in the 24 h following a mechanical overload, and the effect of pharmacological SIRT1 activator SRT1720 on acute chondrocyte injury was assessed. SIRT1 enzymatic activity decreased as early as 5 min following the mechanical overload, and remained suppressed for at least 24 h. The chondrocyte injury response, including apoptosis, oxidative stress, secretion of inflammatory mediators, and alterations in cartilage matrix expression, was prevented with pharmacological activation of SIRT1 in a dose-dependent manner. Overall, the results implicate SIRT1 deactivation as a key molecular event in chondrocyte injury following a mechanical impact overload. As decreased SIRT1 signaling is associated with advanced age, these findings suggest that downregulated SIRT1 activity may be common to both age-related and injury-induced osteoarthritis. |
| first_indexed | 2024-03-11T05:34:40Z |
| format | Article |
| id | doaj.art-35d5cb1ef0204ff19901fe506e832a2b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:34:40Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-35d5cb1ef0204ff19901fe506e832a2b2023-11-17T16:52:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247652110.3390/ijms24076521Decreased SIRT1 Activity Is Involved in the Acute Injury Response of Chondrocytes to Ex Vivo Injurious Mechanical OverloadSonali Karnik0Hessam Noori-Dokht1Taylor Williams2Amin Joukar3Stephen B. Trippel4Uma Sankar5Diane R. Wagner6Department of Mechanical and Energy Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USADepartment of Mechanical and Energy Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USADepartment of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USADepartment of Mechanical and Energy Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USADepartment of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Mechanical and Energy Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USAA better understanding of molecular events following cartilage injury is required to develop treatments that prevent or delay the onset of trauma-induced osteoarthritis. In this study, alterations to SIRT1 activity in bovine articular cartilage explants were evaluated in the 24 h following a mechanical overload, and the effect of pharmacological SIRT1 activator SRT1720 on acute chondrocyte injury was assessed. SIRT1 enzymatic activity decreased as early as 5 min following the mechanical overload, and remained suppressed for at least 24 h. The chondrocyte injury response, including apoptosis, oxidative stress, secretion of inflammatory mediators, and alterations in cartilage matrix expression, was prevented with pharmacological activation of SIRT1 in a dose-dependent manner. Overall, the results implicate SIRT1 deactivation as a key molecular event in chondrocyte injury following a mechanical impact overload. As decreased SIRT1 signaling is associated with advanced age, these findings suggest that downregulated SIRT1 activity may be common to both age-related and injury-induced osteoarthritis.https://www.mdpi.com/1422-0067/24/7/6521chondrocyte injurySIRT1mechanobiologyimpact loadpost-traumatic osteoarthritis |
| spellingShingle | Sonali Karnik Hessam Noori-Dokht Taylor Williams Amin Joukar Stephen B. Trippel Uma Sankar Diane R. Wagner Decreased SIRT1 Activity Is Involved in the Acute Injury Response of Chondrocytes to Ex Vivo Injurious Mechanical Overload International Journal of Molecular Sciences chondrocyte injury SIRT1 mechanobiology impact load post-traumatic osteoarthritis |
| title | Decreased SIRT1 Activity Is Involved in the Acute Injury Response of Chondrocytes to Ex Vivo Injurious Mechanical Overload |
| title_full | Decreased SIRT1 Activity Is Involved in the Acute Injury Response of Chondrocytes to Ex Vivo Injurious Mechanical Overload |
| title_fullStr | Decreased SIRT1 Activity Is Involved in the Acute Injury Response of Chondrocytes to Ex Vivo Injurious Mechanical Overload |
| title_full_unstemmed | Decreased SIRT1 Activity Is Involved in the Acute Injury Response of Chondrocytes to Ex Vivo Injurious Mechanical Overload |
| title_short | Decreased SIRT1 Activity Is Involved in the Acute Injury Response of Chondrocytes to Ex Vivo Injurious Mechanical Overload |
| title_sort | decreased sirt1 activity is involved in the acute injury response of chondrocytes to ex vivo injurious mechanical overload |
| topic | chondrocyte injury SIRT1 mechanobiology impact load post-traumatic osteoarthritis |
| url | https://www.mdpi.com/1422-0067/24/7/6521 |
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