ECTS Abstracts (2015) 1 P208

TNF-[alpha] antagonist infliximab inhibits osteoclast formation of peripheral blood mononuclear cells but does not affect periodontal ligament fibroblast mediated osteoclast formation

Ton Schoenmaker, Teun J de Vries, Yosef Yousovich, Nina Scheres & Vincent Everts

ACTA, University of Amsterdam and VU University, Amsterdam, The Netherlands.

The inflammatory cytokine tumuor necrosis factor-alpha (TNF-α) is elevated in inflamed periodontal tissues and may contribute to periodontitis progression. TNF-α stimulates formation and activity of osteoclasts, the cells that cause alveolar bone degradation and subsequent tooth loss. We previously showed that TNF-α is elevated in co-cultures of periodontal ligament fibroblast (PDLF) and peripheral blood mononuclear cells (PBMC). Hence, TNF-α could be a determining factor in osteoclast formation in these cultures. To assess the role of TNF-α in periodontitis associated osteoclast formation in vitro, osteoclast formation was analysed in the presence of the anti-TNF-α therapeutic agent infliximab in two culture systems: (i) PBMC in co-culture with periodontal ligament fibroblasts from controls and periodontitis patients, or (ii) with PBMC only. The highest level of TNF-α was found in supernatants at day 7 in co-cultures and declined at days 14 and 21 (p < 0.001). TNF-α was undetectable in cultures that received infliximab. The formation and activity of osteoclasts in co-cultures was not affected by infliximab. In contrast, infliximab in cultures of only PBMCs significantly reduced the formation of osteoclasts (p < 0.01). This reduction was accompanied by a decreased number and size of clustered cells, a step that precedes the formation of osteoclasts. Our study shows that the contribution of TNF-α to osteoclast formation is cell system dependent. It contributes to PBMC induced osteoclast formation, possibly by establishing stronger cell-cell interactions that precede osteoclast formation.

Disclosure: The authors declared no competing interests.

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