S-PRG eluate directly suppressed OC-genesis throughout its downregulation of the MAPK/NFATc1 axis, suggesting that S-PRG released from tooth cavity fillings in adjacent periodontal tissue could mitigate the proliferation of OCs in proximal alveolar bone through the release of multiple ions with both therapeutic and prophylactic efficacy on periodontitis. Here, NFATC1 is linked to periodontitis.