Secretion of L-glutamate from osteoclasts through transcytosis
Secretion of L-glutamate from osteoclasts through transcytosis
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DOI：
10.1038/sj.emboj.7601317
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发表时间：
2006-09-20
期刊：
影响因子：
11.4
通讯作者：
Moriyama, Yoshinori
中科院分区：
文献类型：
--
作者：
Morimoto, Riyo;Uehara, Shunsuke;Moriyama, Yoshinori
破骨细胞参与骨基质的分解代谢，并通过胞吞作用消除所产生的降解产物，但胞吞作用的分子机制和调控尚不清楚。在分化过程中，破骨细胞表达谷氨酸囊泡转运蛋白1 (VGLUT1)，这对于谷氨酸在神经元中的囊泡储存和随后的胞吐至关重要。VGLUT1定位于胞囊并积累l -谷氨酸。在KCl或ATP刺激下，破骨细胞以Ca2+依赖的方式分泌l -谷氨酸和骨降解产物。在VGLUT1（-/-）敲除小鼠制备的破骨细胞中，没有依赖kcl和atp的l-谷氨酸分泌。破骨细胞表达mGluR8，一种III类代谢性谷氨酸受体。通过特异性激动剂刺激其抑制l -谷氨酸和骨降解产物的分泌，而通过特异性拮抗剂抑制其刺激骨吸收。最后，我们发现VGLUT1（-/-）小鼠出现骨质疏松。因此，在骨吸收破骨细胞中，l -谷氨酸和骨降解产物通过胞吞作用分泌，释放的l -谷氨酸参与胞吞作用的自调节。谷氨酸信号可能在骨稳态中起重要作用。
Osteoclasts are involved in the catabolism of the bone matrix and eliminate the resulting degradation products through transcytosis, but the molecular mechanism and regulation of transcytosis remain poorly understood. Upon differentiation, osteoclasts express vesicular glutamate transporter 1 (VGLUT1), which is essential for vesicular storage and subsequent exocytosis of glutamate in neurons. VGLUT1 is localized in transcytotic vesicles and accumulates L-glutamate. Osteoclasts secrete L-glutamate and the bone degradation products upon stimulation with KCl or ATP in a Ca2+-dependent manner. KCl-and ATP-dependent secretion of L-glutamate was absent in osteoclasts prepared from VGLUT1(-/-) knockout mice. Osteoclasts express mGluR8, a class III metabotropic glutamate receptor. Its stimulation by a specific agonist inhibits secretion of L-glutamate and bone degradation products, whereas its suppression by a specific antagonist stimulates bone resorption. Finally, it was found that VGLUT1(-/-) mice develop osteoporosis. Thus, in bone-resorbing osteoclasts, L-glutamate and bone degradation products are secreted through transcytosis and the released L-glutamate is involved in autoregulation of transcytosis. Glutamate signaling may play an important role in the bone homeostasis.