In-vivo imaging of the fracture healing in medaka revealed two types of osteoclasts before and after the callus formation by osteoblasts.
In-vivo imaging of the fracture healing in medaka revealed two types of osteoclasts before and after the callus formation by osteoblasts.
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DOI：
10.1016/j.ydbio.2014.08.007
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发表时间：
2014-10
影响因子：
2.7
通讯作者：
Kazuhiro Takeyama;M. Chatani;Y. Takano;A. Kudo
中科院分区：
文献类型：
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作者：
Kazuhiro Takeyama;M. Chatani;Y. Takano;A. Kudo
骨折愈合研究在哺乳动物模型中进行，不仅用于临床应用，而且用于骨代谢，研究表明，通常在诱导破骨细胞进行骨重建之前，先诱导成骨细胞进入骨折部位。然而，破骨细胞和成骨细胞如何以及在何处被诱导仍然是未知的，因为在活体动物中观察破骨细胞和成骨细胞是困难的。为了回答这些问题，我们开发了一种新的骨折愈合模型，使用青鳉。我们在尾鳍鳍条中折断了一侧鳞毛，而没有损伤其他软组织，包括血管。使用转基因青鳉，其中破骨细胞和成骨细胞可视化GFP和DsRed，分别，我们发现，两种不同类型的功能性破骨细胞诱导成骨细胞骨痂形成之前和之后。早期诱导的破骨细胞吸收骨碎片，晚期诱导的破骨细胞重塑骨痂。两种类型的破骨细胞都在血管表面附近诱导，而成骨细胞则从相邻的鳍条迁移。透射电镜观察发现，早期诱导的破骨细胞无明显的皱褶边缘和透明带，而晚期诱导的破骨细胞有透明带，但无典型的皱褶边缘。在骨痂重建过程中，骨折端血管周围cox 2 mRNA表达上调，抑制cox 2表达可抑制晚期破骨细胞的诱导，导致骨折愈合异常。最后，我们开发的青鳉骨折愈合模型为骨折愈合过程中控制细胞行为的分子机制带来了新的见解。
The fracture healing research, which has been performed in mammalian models not only for clinical application but also for bone metabolism, revealed that generally osteoblasts are induced to enter the fracture site before the induction of osteoclasts for bone remodeling. However, it remains unknown how and where osteoclasts and osteoblasts are induced, because it is difficult to observe osteoclasts and osteoblasts in a living animal. To answer these questions, we developed a new fracture healing model by using medaka. We fractured one side of lepidotrichia in a caudal fin ray without injuring the other soft tissues including blood vessels. Using the transgenic medaka in which osteoclasts and osteoblasts were visualized by GFP and DsRed, respectively, we found that two different types of functional osteoclasts were induced before and after osteoblast callus formation. The early-induced osteoclasts resorbed the bone fragments and the late-induced osteoclasts remodeled the callus. Both types of osteoclasts were induced near the surface on the blood vessels, while osteoblasts migrated from adjacent fin ray. Transmission electron microscopy revealed that no significant ruffled border and clear zone were observed in early-induced osteoclasts, whereas the late-induced osteoclasts had clear zones but did not have the typical ruffled border. In the remodeling of the callus, the expression ofcox2 mRNAwas up-regulated at the fracture site around vessels, and the inhibition of Cox2 impaired the induction of the late-induced osteoclasts, resulting in abnormal fracture healing. Finally, our developed medaka fracture healing model brings a new insight into the molecular mechanism for controlling cellular behaviors during the fracture healing.