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P2X4 is Up-regulated in Gingival Fibroblasts after Periodontal Surgery

¹ Department of Oral Biology, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv 69978, Israel;
² Department of Pediatric Hematology-Oncology, The Chaim Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv 52621, Israel;
³ Research Department, Herzog Hospital, Jerusalem, Israel; and
⁴ Department of Prosthodontics, Hebrew University Hadassah School of Dental Medicine, Ein Kerem, Jerusalem, Israel

^* corresponding author, binderma{at}post.tau.ac.il

Several studies have shown that surgical detachment of marginal gingiva close to the cervical cementum of molar teeth in a rat mandible is a distinct stimulus for alveolar bone resorption. Recently, we found that P2X4, an ATP-receptor, is significantly up-regulated in marginal gingival cells soon after surgery. We hypothesized that local release of ATP signaling through P2X4 elicits activation of osteoclasts on the alveolar bone surface. In this study, we identified intense immunoreactivity of gingival fibroblasts to P2X4-specific antibodies and a 6.4-fold increase in expression by real-time RT-PCR. Moreover, a single local application, at the time of surgery, of Apyrase (which degrades ATP) or Coomassie Brilliant Blue (an antagonist of purinoreceptors) significantly reduced alveolar bone loss. We propose that ATP flowing from cells after surgery can directly activate P2X4 receptors in the sensor cells of marginal gingiva through Ca²⁺ signaling, or by direct activation of osteoclasts on the bone surface.

KEY WORDS: P2X4 purinoreceptor • marginal gingival fibroblasts • extracellular ATP • alveolar bone loss • osteoclasts