Melatonin has been implicated in the regulation of bone metabolism; however, the molecular mechanisms underlying its involvement in fracture healing are still obscure. We previously developed an in vivo fracture healing model using the scale of a double-transgenic zebrafish, trap:GFP; osterix:mCherry, which labels osteoclasts and osteoblasts with GFP and mCherry, respectively. Here we show using this model that melatonin inhibits both osteoblast and osteoclast differentiation under fracture stress through the repression of Erk signaling in epidermal cells of the scale. Melatonin treatment resulted in reduced numbers of both osteoblasts and osteoclasts in the fractured scale. Immunochemistry analysis revealed that Erk signals in epidermal cells, which express melatonin receptors, were greatly enhanced in response to fracture stress, but this enhancement was blocked by melatonin treatment. Moreover, inhibition of Erk signaling phenocopied the effects of melatonin treatment in the fractured scale. Collectively, these data suggest that the activation of epidermal Erk signaling is required for both osteoblast and osteoclast differentiation in the early stage of fracture healing, and melatonin suppresses epidermal Erk signaling, leading to impaired fracture healing.

褪黑激素已经参与了骨代谢的调节。然而，其参与骨折愈合的分子机制仍然不清楚。我们以前使用双转基因斑马鱼的规模开发了一个体内骨折愈合模型，trap：GFP ; osterix：mCherry，分别用GFP和mCherry标记破骨细胞和成骨细胞。在这里，我们显示了使用这种模型，褪黑素通过抑制表皮细胞规模的Erk信号传导，在骨折应力下抑制成骨细胞和破骨细胞分化。褪黑素治疗导致骨折规模的成骨细胞和破骨细胞数量减少。免疫化学分析表明，表达褪黑激素受体的表皮细胞中的Erk信号可响应骨折应力而大大增强，但这种增强被褪黑激素处理所阻断。此外，抑制Erk信号表型化了褪黑激素治疗的骨折规模。总的来说，