Amelogenin is recognized as an enamel protein associated with enamel formation. Besides this well-known function, remarkable root resorption has been seen in amelogenin-null mutant mice. Moreover, in vitro culture studies showed that amelogenin suppressed osteoclast differentiation. These studies raised the hypothesis that amelogenin can inhibit root resorption by reducing odontoclast number. To examine this hypothesis, we applied porcine amelogenins in a rat root resorption model, in which maxillary first molars were replanted after being air-dried. Compared with untreated and carrier-treated tooth roots, the application dramatically reduced the odontoclast number on root surfaces and inhibited cementum and root dentin resorption. Amelogenin significantly reduced the number of human odontoclastic cells in culture. It also inhibited RANKL expression in mouse bone marrow cell cultures. All these findings support our hypothesis that amelogenin application suppresses root resorption by inhibiting odontoclast number, and suggest that this is mediated by the regulation of RANKL expression.
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