Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α-Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells
Our recent study detected the expression of a tissue renin–angiotensin system (tRAS) in human intervertebral discs (IVDs). The present study sought to investigate the impact of the angiotensin II receptor type 1 (AGTR1) antagonist losartan on human nucleus pulposus (NP) cell inflammation and degener...
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MDPI AG
2021-01-01
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| Online Access: | https://www.mdpi.com/2076-3417/11/1/417 |
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| author | Babak Saravi Zhen Li Judith Pfannkuche Laura Wystrach Sonja Häckel Christoph E. Albers Sibylle Grad Mauro Alini Robert Geoffrey Richards Corinna Lang Norbert Südkamp Hagen Schmal Gernot Lang |
| author_facet | Babak Saravi Zhen Li Judith Pfannkuche Laura Wystrach Sonja Häckel Christoph E. Albers Sibylle Grad Mauro Alini Robert Geoffrey Richards Corinna Lang Norbert Südkamp Hagen Schmal Gernot Lang |
| author_sort | Babak Saravi |
| collection | DOAJ |
| description | Our recent study detected the expression of a tissue renin–angiotensin system (tRAS) in human intervertebral discs (IVDs). The present study sought to investigate the impact of the angiotensin II receptor type 1 (AGTR1) antagonist losartan on human nucleus pulposus (NP) cell inflammation and degeneration induced by tumor necrosis factor-α (TNF-α). Human NP cells (4 donors; Pfirrmann grade 2–3; 30–37-years–old; male) were isolated and expanded. TNF-α (10 ng/mL) was used to induce inflammation and degeneration. We examined the impact of losartan supplementation and measured gene expression of tRAS, anabolic, catabolic, and inflammatory markers in NP cells after 24 and 72 h of exposure. T0070907, a PPAR gamma antagonist, was applied to examine the regulatory pathway of losartan. Losartan (1 mM) significantly impaired the TNF-α-induced increase of pro-inflammatory (nitric oxide and TNF-α), catabolic (matrix metalloproteinases), and tRAS (AGTR1a and angiotensin-converting enzyme) markers. Further, losartan maintained the NP cell phenotype by upregulating aggrecan and downregulating collagen type I expression. In summary, losartan showed anti-inflammatory, anti-catabolic, and positive phenotype-modulating effects on human NP cells. These results indicate that tRAS signaling plays an important role in IVD degeneration, and tRAS modulation with losartan could represent a novel therapeutic approach. |
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| language | English |
| last_indexed | 2024-03-10T13:30:10Z |
| publishDate | 2021-01-01 |
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| series | Applied Sciences |
| spelling | doaj.art-9736723ab134477d88e6fbff9a79edc32023-11-21T08:05:38ZengMDPI AGApplied Sciences2076-34172021-01-0111141710.3390/app11010417Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α-Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus CellsBabak Saravi0Zhen Li1Judith Pfannkuche2Laura Wystrach3Sonja Häckel4Christoph E. Albers5Sibylle Grad6Mauro Alini7Robert Geoffrey Richards8Corinna Lang9Norbert Südkamp10Hagen Schmal11Gernot Lang12AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, SwitzerlandAO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, SwitzerlandAO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, SwitzerlandDepartment of Orthopedics and Trauma Surgery, Medical Centre—Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetterstrasse 55, 79106 Freiburg, GermanyDepartment of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 18, 3010 Bern, SwitzerlandDepartment of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 18, 3010 Bern, SwitzerlandAO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, SwitzerlandAO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, SwitzerlandAO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, SwitzerlandDepartment of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, GermanyDepartment of Orthopedics and Trauma Surgery, Medical Centre—Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetterstrasse 55, 79106 Freiburg, GermanyDepartment of Orthopedics and Trauma Surgery, Medical Centre—Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetterstrasse 55, 79106 Freiburg, GermanyDepartment of Orthopedics and Trauma Surgery, Medical Centre—Albert-Ludwigs-University of Freiburg, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetterstrasse 55, 79106 Freiburg, GermanyOur recent study detected the expression of a tissue renin–angiotensin system (tRAS) in human intervertebral discs (IVDs). The present study sought to investigate the impact of the angiotensin II receptor type 1 (AGTR1) antagonist losartan on human nucleus pulposus (NP) cell inflammation and degeneration induced by tumor necrosis factor-α (TNF-α). Human NP cells (4 donors; Pfirrmann grade 2–3; 30–37-years–old; male) were isolated and expanded. TNF-α (10 ng/mL) was used to induce inflammation and degeneration. We examined the impact of losartan supplementation and measured gene expression of tRAS, anabolic, catabolic, and inflammatory markers in NP cells after 24 and 72 h of exposure. T0070907, a PPAR gamma antagonist, was applied to examine the regulatory pathway of losartan. Losartan (1 mM) significantly impaired the TNF-α-induced increase of pro-inflammatory (nitric oxide and TNF-α), catabolic (matrix metalloproteinases), and tRAS (AGTR1a and angiotensin-converting enzyme) markers. Further, losartan maintained the NP cell phenotype by upregulating aggrecan and downregulating collagen type I expression. In summary, losartan showed anti-inflammatory, anti-catabolic, and positive phenotype-modulating effects on human NP cells. These results indicate that tRAS signaling plays an important role in IVD degeneration, and tRAS modulation with losartan could represent a novel therapeutic approach.https://www.mdpi.com/2076-3417/11/1/417intervertebral discrenin–angiotensin systemdegenerationregenerationspineinflammation |
| spellingShingle | Babak Saravi Zhen Li Judith Pfannkuche Laura Wystrach Sonja Häckel Christoph E. Albers Sibylle Grad Mauro Alini Robert Geoffrey Richards Corinna Lang Norbert Südkamp Hagen Schmal Gernot Lang Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α-Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells Applied Sciences intervertebral disc renin–angiotensin system degeneration regeneration spine inflammation |
| title | Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α-Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells |
| title_full | Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α-Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells |
| title_fullStr | Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α-Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells |
| title_full_unstemmed | Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α-Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells |
| title_short | Angiotensin II Type 1 Receptor Antagonist Losartan Inhibits TNF-α-Induced Inflammation and Degeneration Processes in Human Nucleus Pulposus Cells |
| title_sort | angiotensin ii type 1 receptor antagonist losartan inhibits tnf α induced inflammation and degeneration processes in human nucleus pulposus cells |
| topic | intervertebral disc renin–angiotensin system degeneration regeneration spine inflammation |
| url | https://www.mdpi.com/2076-3417/11/1/417 |
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