Substance P aggravates ligature-induced periodontitis in mice

Periodontitis is one of the most common oral diseases in humans, affecting over
40% of adult Americans. Pain-sensing nerves, or nociceptors, sense local
environmental changes and often contain neuropeptides. Recent studies have
suggested that nociceptors magnify host response and regulate bone loss in the
periodontium. A subset of nociceptors projected to periodontium contains
neuropeptides, such as calcitonin gene-related peptide (CGRP) or substance P
(SP). However, the specific roles of neuropeptides from nociceptive neural
terminals in periodontitis remain to be determined. In this study, we
investigated the roles of neuropeptides on host responses and bone loss in
ligature-induced periodontitis. Deletion of tachykinin precursor 1 (Tac1), a gene
that encodes SP, or treatment of gingiva with SP antagonist significantly reduced
bone loss in ligature-induced periodontitis, whereas deletion of calcitonin
related polypeptide alpha (Calca), a gene that encodes CGRP, showed a
marginal role on bone loss. Ligature-induced recruitment of leukocytes,
including neutrophils, and increase in cytokines leading to bone loss in
periodontium was significantly less in Tac1 knockout mice. Furthermore, intragingival
injection of SP, but not neurokinin A, induced a vigorous inflammatory
response and osteoclast activation in alveolar bone and facilitated bone loss in
ligature-induced periodontitis. Altogether, our data suggest that SP plays
significant roles in regulating host responses and bone resorption in ligatureinduced
periodontitis.