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Inflammatory interactions between degenerated intervertebral discs and microglia: Implication of sphingosine‐1‐phosphate signaling
Author(s) -
Navone Stefania E.,
Campanella Rolando,
Guarnaccia Laura,
Ouellet Jean A.,
Locatelli Marco,
Cordiglieri Chiara,
Gualtierotti Roberta,
Gaudino Chiara,
Ciniglio Appiani Giuseppe,
Luzzi Sabino,
Borsa Stefano,
Rampini Paolo,
Pluderi Mauro,
Haglund Lisbet,
Riboni Laura,
Alini Mauro,
Marfia Giovanni
Publication year - 2021
Publication title -
journal of orthopaedic research®
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.24827
Subject(s) - microglia , intervertebral disc , microbiology and biotechnology , sphingosine , sphingosine 1 phosphate , chemistry , chemotaxis , crosstalk , cytokine , inflammation , pathology , biology , anatomy , medicine , immunology , biochemistry , receptor , physics , optics
The etiology of intervertebral disc degeneration is largely unknown, but local neuroinflammation may exert a crucial role through activation of cells as microglia and pro‐inflammatory cytokines production. We aimed to compare the effect of degenerated and normal intervertebral disc microenvironment on microglial cells and the potential role of sphingosine‐1‐phosphate, a pro‐inflammatory sphingolipid, in their crosstalk. Human degenerated intervertebral discs (Pfirrmann grade IV) were obtained at surgery for spondylolisthesis. Normal intervertebral discs were collected from cadaveric normal lumbar spines. Normal and degenerated‐intervertebral discs were kept in culture to obtain media conditioning. Then, microglial cells were cocultured with conditioned media and viability, proliferation, migration, chemotaxis, and inflammatory gene expression were evaluated. The results demonstrate that conditioned media from degenerated intervertebral discs activate microglial cells, increasing chemotaxis, migration, and pro‐inflammatory mediators release to a great extent than normal discs. In addition, we show that the administration of sphingosine‐1‐phosphate to normal intervertebral disc/microglia coculture mimicked degenerative effects. Interestingly, sphingosine‐1‐phosphate content in conditioned media from degenerated discs was significantly higher than that from normal ones. In addition, FTY720, a functional antagonist of sphingosine‐1‐phosphate, potently inhibited the effect of degenerated intervertebral discs on microglial inflammatory factor transcription and migration. Our data report, for the first time, that sphingosine‐1‐phosphate is involved as signal in the microenvironment of human degenerated intervertebral discs. Sphingosine‐1‐phosphate signaling modulation by FTY720 may induce beneficial effects in counteracting microglial activation during intervertebral disc degeneration.