Abstract
ABSTRACTInflammatory cytokines play an important role in intervertebral disc degeneration. Although largely produced by immune cells, nucleus pulposus (NP) cells can also secrete them under various conditions, for example, under free swelling. Thus, tissue hypotonicity may be an inflammatory trigger for NP cells. The aim of this study was to investigate whether decreased tonicity under restricted swelling conditions (as occurring in early disc degeneration) could initiate an inflammatory cascade that mediates further degeneration. Healthy bovine NP tissue was balanced against different PEG concentrations (0–30%) to obtain various tissue tonicities. Samples were then placed in an artificial annulus (fixed volume) and were cultured for 3, 7, or 21 days, with free swelling NP as control. Tissue content (water, glycosaminoglycan, collagen) was analyzed, and both the tissue and medium were screened for tumor necrosis factor alpha (TNF‐α), interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), prostaglandin‐E2 (PGE2), and nitric oxide (NO). A range of tonicities (isotonic to hypotonic) was present at day 3 in the PEG‐treated samples. However, during culture, the tonicity range narrowed as GAGs leached from the tissue. TNF‐α and IL‐1β were below detection limits in all conditions, while mid‐ and downstream inflammatory cytokines were detected. This may suggest that the extracellular environment directly affects NP cells instead of inducing a classical inflammatory cascade. Furthermore, IL‐8 increased in swelling restricted samples, while IL‐6 and PGE2 were elevated in free swelling controls. These findings may suggest the involvement of different mechanisms in disc degeneration with intact AF compared to herniation, and encourage further investigation. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res
Highlights
Inflammatory cytokines play an important role in intervertebral disc degeneration
Inflammation is most profound after herniation, pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-a), interleukin-1b (IL-1b), interleukin-6 (IL-6), and prostaglandin-E2 (PGE2), are detected in nucleus pulposus (NP) tissue without herniation,[10,11,12,13,14] suggesting a crucial role of inflammation in the process of disc degeneration.[6,15]
These results suggest that different processes may be activated in NP tissue in degenerating discs compared to herniated discs
Summary
Inflammatory cytokines play an important role in intervertebral disc degeneration. largely produced by immune cells, nucleus pulposus (NP) cells can secrete them under various conditions, for example, under free swelling. IL-8 increased in swelling restricted samples, while IL-6 and PGE2 were elevated in free swelling controls These findings may suggest the involvement of different mechanisms in disc degeneration with intact AF compared to herniation, and encourage further investigation. The metabolism of the NP cells is altered, resulting in a decrease in proteoglycan and collagen type II synthesis, and an increase in collagen type I synthesis, metalloproteinase (MMP) activity, and/or a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) activity.[6] the fixed charge density generated by the negatively charged chondroitin and keratan sulfate groups of the proteoglycans is reduced This reduction impairs the overall swelling pressure and the load-bearing capacity of the NP, resulting in a loss of disc height and overloading of the AF. The presence of inflammatory factors seems to be related to pain in an early stage of disc degeneration when the AF is still intact, the socalled discogenic pain.[6]
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