Autophagy in osteoblasts is involved in mineralization and bone homeostasis
Autophagy in osteoblasts is involved in mineralization and bone homeostasis
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DOI：
10.4161/auto.36182
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发表时间：
2014-11-01
期刊：
影响因子：
13.3
通讯作者：
Pierrefite-Carle, Valerie
中科院分区：
文献类型：
--
作者：
Nollet, Marie;Santucci-Darmanin, Sabine;Pierrefite-Carle, Valerie
骨重建是一种严格控制的机制，其中成骨细胞（OB），负责骨形成的细胞，破骨细胞（OC），专门用于骨吸收的细胞，和骨细胞，嵌入骨基质中的多功能机械传感细胞，是主要的演员。OB中氧化应激的增加与骨质疏松症的发展有关，但自噬在OB中的作用尚未得到解决。这就是本研究的目标。我们首先表明，自噬过程中诱导成骨细胞矿化。然后，通过敲低自噬必需基因和OB特异性自噬缺陷小鼠，我们证明了自噬缺陷降低了矿化能力。此外，我们的数据表明，自噬空泡可以作为车辆在OB分泌磷灰石晶体。此外，自噬缺陷的OB表现出增加的氧化应激和NFKB 1受体激活剂（TNFSF 11/RANKL）的分泌，有利于OC的产生，OC是专门从事骨吸收的细胞。在体内，我们观察到OB特异性自噬缺陷小鼠的骨小梁质量减少了50%。两者合计，我们的研究结果表明，第一次在OB的自噬参与矿化过程和骨稳态。这些发现对于从珊瑚到脊椎动物的矿化组织具有重要意义，并为钙化组织相关的代谢病变发现了新的治疗靶点。
Bone remodeling is a tightly controlled mechanism in which osteoblasts (OB), the cells responsible for bone formation, osteoclasts (OC), the cells specialized for bone resorption, and osteocytes, the multifunctional mechanosensing cells embedded in the bone matrix, are the main actors. Increased oxidative stress in OB, the cells producing and mineralizing bone matrix, has been associated with osteoporosis development but the role of autophagy in OB has not yet been addressed. This is the goal of the present study. We first show that the autophagic process is induced in OB during mineralization. Then, using knockdown of autophagy-essential genes and OB-specific autophagy-deficient mice, we demonstrate that autophagy deficiency reduces mineralization capacity. Moreover, our data suggest that autophagic vacuoles could be used as vehicles in OB to secrete apatite crystals. In addition, autophagy-deficient OB exhibit increased oxidative stress and secretion of the receptor activator of NFKB1 (TNFSF11/RANKL), favoring generation of OC, the cells specialized in bone resorption. In vivo, we observed a 50% reduction in trabecular bone mass in OB-specific autophagy-deficient mice. Taken together, our results show for the first time that autophagy in OB is involved both in the mineralization process and in bone homeostasis. These findings are of importance for mineralized tissues which extend from corals to vertebrates and uncover new therapeutic targets for calcified tissue-related metabolic pathologies.