## 1 Introduction  
Low back pain (LBP) is one of the most common health problems and a leading cause of disability worldwide, resulting in an enormous socioeconomic burden [1]. Symptomatic intervertebral disc degeneration (IDD) is a major cause of LBP [2]. IDD is associated with extracellular matrix (ECM) degradation, the release of pro-inflammatory cytokines, alterations in spine biomechanics, increased angiogenesis, and neo-innervation, resulting in disogenic pain and disability [3, 4]. Pro-inflammatory cytokines affect the production of relevant catabolic enzymes, leading to progressive ECM degeneration. Several studies have shown that pro-inflammatory markers, such as tumor necrosis factor-alpha (TNF-\(\alpha\)) and interleukin (IL)-6, are increasingly expressed in degenerated human IVDs [4, 5].  
At present, none of the available treatment strategies address the actual underlying pathologic dysregulations leading to IDD. Affected patients in the early stages of IVD degeneration and not qualified for surgery do not benefit from conservative treatments [6]. Surgical strategies that include spinal fusion or total disc replacement (TDR) have been introduced and carried out to treat symptomatic patients, even though the long-term benefit is elusive compared with conservative treatment options [7, 8, 9, 10]. Given the dearth of adequate self-repair capabilities of IVDs and satisfactory treatment approaches, new biomolecular therapies targeting the inflammatory and degenerative cycles are receiving attention [11]. These approaches attempt to reduce the inflammatory settings of degenerative and inflammatory IVDs in order to slow down the progressive pro-inflammatory cascade [12, 13, 14, 15].  
Recently, we showed that the tissue renin-angiotensin system (tRAS) is expressed in human IVDs, revealing a positive correlation with pro-inflammatory cytokines and catabolic enzymes [16]. Angiotensin II (AngII) is the major effector of the tRAS and is involved in inflammatory cell pathways. Angiotensin (ATG), its precursor protein, is cleaved by the protease renin to produce AngI, which is then converted to biologically active AngII by angiotensin-converting enzyme (ACE). RAS inhibitors are one of the most prescribed drugs globally [17]. Recent research has raised evidence that RAS inhibitors could reduce TNF-\(\alpha\) production both in vitro and in vivo [18, 19]. [PERSON] et al. showed in a rat model of rheumatoid arthritis (RA) that TNF-\(\alpha\) production and pathological characteristics, such as knee joint swelling, were significantly diminished by ACE inhibitor application [20]. These findings were also confirmed by other groups, revealing that ACE inhibitors and angiotensin II receptor type 1 blockers (ARBs) are associated with anti-arthritic effects through the reduction of reactive oxygen species, inflammation, neutrophil recruitment, disease activity, and finally joint destruction [21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34]. Moreover, animal models of renal injury examining the protective impact of RAS inhibitors revealed that inhibition of AngII functions via ACE inhibitors or ARBs reduced the recruitment of pro-inflammatory cells and catabolic gene expression [35, 36, 37].  
We hypothesize that a local RAS is involved in the progress of disc degeneration, inflammation, and discogenic pain in human IVD cells. As inflammation contributes to IDD, the present study sought to investigate whether inhibition of the angiotensin II receptor type 1 (AGTR1) would have a protective effect on IVD tissue biology. Specifically, we investigated the potential protective effects of angiotensin II receptor type 1 antagonist losartan on human nucleus pulposus (NP) cell inflammation and degeneration induced by TNF-\(\alpha\).