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To study this process, we examined host-microbial interactions in the context of the periodontium <jats:italic>via<\/jats:italic> molecular and functional cell assays and showed that human PDL cell interactions with <jats:italic>Treponema denticola<\/jats:italic> induce actin depolymerization through a novel actin reorganization signaling mechanism. This actin reorganization mechanism and loss of cell adhesion is a pathological response characterized by an initial upregulation of RASA4 mRNA expression resulting in an increase in matrix metalloproteinase-2 activity. This mechanism is specific to the <jats:italic>T.\u00a0denticola<\/jats:italic> effector protein, dentilisin, thereby uncovering a novel effect for <jats:italic>Treponema denticola<\/jats:italic>-mediated RASA4 transcriptional activation and actin depolymerization in primary human PDL cells.<\/jats:p>","DOI":"10.3389\/fcimb.2021.671968","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T15:05:13Z","timestamp":1621436713000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Treponema denticola-Induced RASA4 Upregulation Mediates Cytoskeletal Dysfunction and MMP-2 Activity in Periodontal Fibroblasts"],"prefix":"10.3389","volume":"11","author":[{"given":"Erin Trent","family":"Malone","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Ganther","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nevina","family":"Mena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allan","family":"Radaic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keemia","family":"Shariati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail","family":"Kindberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Tafolla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pachiyappan","family":"Kamarajan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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