Osteoclastic and Osteoblastic Responses to Hypergravity and Microgravity: Analysis Using Goldfish Scales as a Bone Model
Osteoclastic and Osteoblastic Responses to Hypergravity and Microgravity: Analysis Using Goldfish Scales as a Bone Model
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DOI：
10.2108/zs210107
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发表时间：
2022-04
影响因子：
0.9
通讯作者：
Tatsuki Yamamoto;M. Ikegame;Yukihiro Furusawa;Y. Tabuchi;Kaito Hatano;Kazuki Watanabe;Umi Kawago;J. Hirayama;S. Yano;T. Sekiguchi;K. Kitamura;M. Endo;Arata Nagami;H. Matsubara;Yusuke Maruyama;A. Hattori;N. Suzuki
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作者：
Tatsuki Yamamoto;M. Ikegame;Yukihiro Furusawa;Y. Tabuchi;Kaito Hatano;Kazuki Watanabe;Umi Kawago;J. Hirayama;S. Yano;T. Sekiguchi;K. Kitamura;M. Endo;Arata Nagami;H. Matsubara;Yusuke Maruyama;A. Hattori;N. Suzuki
众所周知，骨基质在对超重力和微重力等物理应力的反应中起着重要的作用。为了准确分析骨对超重力和微重力的响应，迫切需要一种破骨细胞、成骨细胞和骨基质共存条件下的培养体系。硬骨鳞片是一种独特的钙化器官，破骨细胞、成骨细胞和两层骨基质，即骨层和纤维层共存。因此，我们利用金鱼鳞建立了破骨细胞和成骨细胞与完整骨基质的体外器官培养体系。采用比例尺培养系统，研究离心机超重力和三维回转器模拟地面微重力(g-µG)对破骨细胞和成骨细胞的影响。3重力(3g)作用1d后，破骨细胞标志物基因表达水平降低，成骨细胞标志物基因表达增强。暴露1d后，模拟g-µG诱导破骨细胞标志物基因表达显著增强，而成骨细胞标志物基因表达降低。破骨细胞在这些重力刺激下发生了主要的形态变化。通过模拟g-µG处理，诱导了形态上的破骨细胞激活，而在3G处理的鳞片中观察到了破骨细胞的失活。在空间实验中，重现了用模拟g-µG获得的结果。RNA测序分析表明，在飞行微重力条件下，Wnt信号的下调诱导了破骨细胞的激活。因此，金鱼鳞片可以作为骨模型来分析破骨细胞和成骨细胞对重力的反应。
It is known that the bone matrix plays an important role in the response to physical stresses such as hypergravity and microgravity. In order to accurately analyze the response of bone to hypergravity and microgravity, a culture system under the conditions of coexistence of osteoclasts, osteoblasts, and bone matrix was earnestly desired. The teleost scale is a unique calcified organ in which osteoclasts, osteoblasts, and the two layers of bone matrix, i.e., a bony layer and a fibrillary layer, coexist. Therefore, we have developed in vitro organ culture systems of osteoclasts and osteoblasts with the intact bone matrix using goldfish scales. Using the scale culture system, we examined the effects of hypergravity with a centrifuge and simulated ground microgravity (g-µG) with a three-dimensional clinostat on osteoclasts and osteoblasts. Under 3-gravity (3G) loading for 1 day, osteoclastic marker mRNA expression levels decreased, while the mRNA expression of the osteoblastic marker increased. Upon 1 day of exposure, the simulated g-µG induced remarkable enhancement of osteoclastic marker mRNA expression, whereas the osteoblastic marker mRNA expression decreased. In response to these gravitational stimuli, osteoclasts underwent major morphological changes. By simulated g-µG treatments, morphological osteoclastic activation was induced, while osteoclastic deactivation was observed in the 3G-treated scales. In space experiments, the results that had been obtained with simulated g-µG were reproduced. RNA-sequencing analysis showed that osteoclastic activation was induced by the down-regulation of Wnt signaling under flight-microgravity. Thus, goldfish scales can be utilized as a bone model to analyze the responses of osteoclasts and osteoblasts to gravity.