Strain Deprivation of Gingival Fibroblasts Signals Alveolar Bone Remodeling

Several studies have shown that surgical detachment of marginal gingival close to the cervical cementum of molar teeth in a rat mandible is a distinct stimulus for alveolar bone resorption. Recently, we have demonstrated that extracellular ATP flowing from cells immediately after surgery can directly activate P2X4 purinoreceptors in marginal gingival fibroblasts through calcium signaling and activation of osteoclasts on bone surface. Our hypothesis is that deprivation of normal strain of gingival fibroblasts, shrinks cells and mechanically deforms membranes results in ATP release stimulating a purinoreceptor pathway cascade resulting in alveolar bone resorption. "Objectives:", The objective of the present study is to evaluate key determinants involved in this process. "Methods:", A coronal surgical approach included the separation of the marginal gingival from roots of molar teeth in Wistar rats, using a small periostal elevator. At time of surgery, several drugs which are known to affect cell shape, cytoskeleton and ionic fluxes were applied locally at the surgical site. 21 days later the rats were sacrificed and microradiography was performed on 1.5mm thick mandible cross sections. "Results:", We found that lowering locally the calcium reduced the amount of bone loss. Also, drugs like orthovanadate or H-7 which inhibit the ability of cells to contract reduced significantly alveolar bone loss. PPADS (pyridoxal phosphate-6-azophenyl-2'-4' disulphonic acid) a P2X antagonist significantly reduced alveolar bone loss.Local application at time of surgery of Apyrase which degrades ATP or Coomasie Brilliant Blue, antagonists of purinoreceptors reduced significantly alveolar bone loss. "Conclusions:", We conclude that ATP flowed out can act between sensor cells and bone cells through Ca+2 signaling or by direct activation of osteoclastic bone resorption. By changing normal tension-integrity of marginal gingival fibroblasts adaptive remodeling of alveolar bone occurs. Also, new modes of local therapeutic intervention to prevent alveolar bone loss are proposed.