期刊
APPLIED SCIENCES-BASEL
卷 11, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/app11010417
关键词
intervertebral disc; renin-angiotensin system; degeneration; regeneration; spine; inflammation
类别
资金
- German Spine Society (DWG)
- German Arthritis Foundation (DAH)
- Foundation for the Promotion of Alternate and Complementary Methods to Reduce Animal Testing (SET) under the project InflamoDisc [59]
- AO Foundation
- AOSpine International
- Berta-Ottenstein Programme for Advanced Clinician Scientists, Faculty of Medicine, University of Freiburg
The study found that losartan had anti-inflammatory, anti-catabolic, and positive phenotype-modulating effects on human nucleus pulposus cells, indicating the important role of tRAS signaling in intervertebral disc degeneration.
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-alpha (TNF-alpha). Human NP cells (4 donors; Pfirrmann grade 2-3; 30-37-years-old; male) were isolated and expanded. TNF-alpha (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-alpha-induced increase of pro-inflammatory (nitric oxide and TNF-alpha), 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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