Csf1 Signaling Regulates Maintenance of Resident Macrophages and Bone Formation in the Mouse Cochlea
Csf1 Signaling Regulates Maintenance of Resident Macrophages and Bone Formation in the Mouse Cochlea
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DOI：
10.3389/fneur.2019.01244
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发表时间：
2019-11-21
影响因子：
3.4
通讯作者：
Kishimoto, Ippei
中科院分区：
文献类型：
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作者：
Okano, Takayuki;Kishimoto, Ippei
在哺乳动物的耳蜗里，即使在稳定状态下，驻留的巨噬细胞也会聚集在螺旋韧带、螺旋神经节和血管纹中。据信，内耳损伤后，内耳中驻留的巨噬细胞维持内耳的动态平衡，并作为前线防御的一部分变得活跃。然而，蜗居巨噬细胞的确切作用还需要进一步澄清。集落刺激因子-1(CSF1)信号调节驻留巨噬细胞的存活、增殖和分化，对内耳驻留巨噬细胞似乎是必不可少的。为了研究CSF1信号在听觉功能中的作用，我们研究了CSF1纯合子突变(CSF1(OP/OP))小鼠的听小骨和内耳。CSF1(OP/OP)小鼠的听小骨，包括砧骨和砧骨，肉眼可见骨质增厚，内耳的耳囊也厚而不透明。组织学分析表明，CSF1(OP/OP)小鼠耳囊增厚，表现为松质骨变性。对4周龄CSF1(OP/OP)小鼠听性脑干反应的测量表明，与野生型小鼠相比，CSF1(OP/OP)小鼠的听性脑干反应阈值显著提高，这表明CSF1(OP/OP)小鼠表现出听力损失，至少部分原因是内耳的听小骨和骨囊畸形。此外，CSF1(OP/OP)小鼠螺旋韧带和血管纹中驻留的巨噬细胞数量不足，但螺旋神经节中的驻留巨噬细胞数量不少。这些数据证明，CSF1信号不仅对内耳的骨形成很重要，而且对成年小鼠耳蜗螺旋韧带和血管纹中驻留的巨噬细胞的维持也很重要。
In the mammalian cochlea, resident macrophages settle in the spiral ligament, spiral ganglion, and stria vascularis, even at the steady state. Resident macrophages in the cochlea are believed to maintain homeostasis in the inner ear and become active, as part of the front line defense, following inner ear damage. However, the exact roles of cochlear resident macrophages require further clarification. Colony stimulating factor-1 (Csf1) signaling regulates survival, proliferation, and differentiation of resident macrophages and appears to be essential for resident macrophages in the inner ear. To examine the roles of Csf1 signaling in auditory function, we examined the ossicles and inner ear of homozygous Csf1 mutant (Csf1(op/op)) mice. The ossicles including the incus and stapes of Csf1(op/op) mice macroscopically demonstrated bone thickening, and the otic capsules of the inner ear were also thick and opaque. Histological analyses demonstrated that the otic capsules in Csf1(op/op) mice were thickened and showed spongy bone degeneration. Measurements of the auditory brainstem response revealed significant elevation of thresholds in 4-week old Csf1(op/op) mice compared with wild-type littermates, indicating that Csf1(op/op) mice demonstrate hearing loss due to, at least in part, deformity of the ossicles and bone capsule of the inner ear. Furthermore, Csf1(op/op) mice are deficient in the number of resident macrophages in the spiral ligament and stria vascularis, but not in the spiral ganglion. These data provide evidence that Csf1 signaling is important not only for bone formation in the inner ear, but also for the maintenance of resident macrophages in the spiral ligament and stria vascularis in the adult mouse cochlea.