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This study was designed to observe the expression of important hedgehog (Hh) signal factors in the bone tissue of rats with chronic fluorosis and cultured osteoblasts in order to investigate the role and significance of the Hh signal in fluoride-induced bone injury. Healthy Sprague-Dawley (SD) rats were randomly divided into four groups the control group, the fluorosis group (F Group), the fluoride + blocker group (F + Cycl group rats were treated with fluoride + cyclopamine), and the fluoride + blocker control group (F + DMSO group). After