Graciosa Q. Teixeira, Zhiyao Yong, Amelie Kuhn, Jana Riegger, Raquel M. Goncalves, Michael Ruf, Uwe M. Mauer, Markus Huber-Lang, Anita Ignatius, Rolf E. Brenner, Cornelia Neidlinger-Wilke

June 2021, pp 1 - 10 Original Article Read Full Article 10.1007/s00586-021-06901-5

First Online: 24 June 2021


Formation of terminal complement complex (TCC), a downstream complement system activation product inducing inflammatory processes and cell lysis, has been identified in degenerated discs. However, it remains unclear which molecular factors regulate complement activation during disc degeneration (DD). This study investigated a possible involvement of the pro-inflammatory cytokine interleukin-1β (IL-1β) and the lysosomal protease cathepsin D (CTSD).


Disc biopsies were collected from patients suffering from DD (n = 43) and adolescent idiopathic scoliosis (AIS, n = 13). Standardized tissue punches and isolated cells from nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) were stimulated with 5% human serum (HS) alone or in combination with IL-1β, CTSD or zymosan. TCC formation and modulation by the complement regulatory proteins CD46, CD55 and CD59 were analysed.


In DD tissue cultures, IL-1β stimulation decreased the percentage of TCC + cells in AF and EP (P


These results suggest a functional relevance of IL-1β and CTSD in modulating TCC formation in DD, with differences between tissue regions. Although strong TCC deposition may represent a degeneration-associated event, IL-1β may inhibit it. In contrast, TCC formation was shown to be triggered by CTSD, indicating a multifunctional involvement in disc pathophysiology.

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