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 sought to investigate impact angiotensin II receptor type 1 (AGTR1) antagonist losartan on 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 expanded. TNF-α (10 ng/mL) was used induce degeneration. We examined supplementation measured gene tRAS, anabolic, catabolic, inflammatory markers after 24 72 h exposure. T0070907, PPAR gamma antagonist, applied examine regulatory pathway losartan. Losartan (1 mM) significantly impaired TNF-α-induced increase pro-inflammatory (nitric oxide TNF-α), catabolic (matrix metalloproteinases), tRAS (AGTR1a angiotensin-converting enzyme) markers. Further, maintained phenotype upregulating aggrecan downregulating collagen I expression. In summary, showed anti-inflammatory, anti-catabolic, positive phenotype-modulating effects cells. These results indicate that signaling plays an important role IVD degeneration, modulation with could represent novel therapeutic approach.