Role of Scx+/Sox9+ cells as potential progenitor cells for postnatal supraspinatus enthesis formation and healing after injury in mice.

Role of Scx+/Sox9+ cells as potential progenitor cells for postnatal supraspinatus enthesis formation and healing after injury in mice.
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DOI:
10.1371/journal.pone.0242286
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发表时间:
2020
期刊:
影响因子:
3.7
通讯作者:
Miyamoto T
Miyamoto T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ideo K;Tokunaga T;Shukunami C;Takimoto A;Yoshimoto Y;Yonemitsu R;Karasugi T;Mizuta H;Hiraki Y;Miyamoto T

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共表达碱性螺旋环螺旋转录因子scleraxis(Scx)和SRY盒9(Sox 9)的多能细胞群已被证明有助于在小鼠胚胎发育过程中建立附着点(肌腱附着位点)。本研究的目的是调查Scx+/Sox 9+细胞在出生后形成的纤维软骨附着点和损伤后的愈合过程中的参与,使用ScxGFP转基因小鼠。我们证明,Scx+/Sox 9+细胞定位于层在插入部位在产后形成的纤维软骨附着点冈上肌腱,直到产后3周。此外,这些细胞在出生后6周时很少见,此时成熟的纤维软骨附着点形成。此外,我们研究了Scx+/Sox 9+细胞在冈上肌腱止点损伤后愈合过程中的参与,比较了20周龄和3周龄小鼠的反应。在20周龄的纤维血管组织紊乱的小鼠对损伤的反应的愈合过程中,少量Scx+/Sox 9+细胞从损伤后1周开始短暂出现,但在损伤后4周时很少见到。同时,3周龄小鼠在损伤后4周,在愈合的末端形成一薄层纤维软骨组织,并伴有钙化。伤后1 ~ 2周,Scx+/Sox 9+细胞较20周龄小鼠增多,且广泛分布于损伤部位。损伤后4周,这些细胞位于重建的纤维软骨层表面附近。在我们的3周龄小鼠模型中,Scx+/Sox 9+细胞在损伤的附着点处的时空定位模式与出生后纤维软骨附着点形成中的时空定位模式相似。这些结果表明,Scx+/Sox 9+细胞可能有一个作用,作为附着点祖细胞样细胞在出生后成熟的纤维软骨附着点和愈合后损伤的方式类似于胚胎发育中所看到的。
A multipotent cell population co-expressing a basic-helix-loop-helix transcription factor scleraxis (Scx) and SRY-box 9 (Sox9) has been shown to contribute to the establishment of entheses (tendon attachment sites) during mouse embryonic development. The present study aimed to investigate the involvement of Scx+/Sox9+ cells in the postnatal formation of fibrocartilaginous entheses and in the healing process after injury, using ScxGFP transgenic mice. We demonstrate that Scx+/Sox9+ cells are localized in layers at the insertion site during the postnatal formation of fibrocartilaginous entheses of supraspinatus tendon until postnatal 3 weeks. Further, these cells were rarely seen at postnatal 6 weeks, when mature fibrocartilaginous entheses were formed. Furthermore, we investigated the involvement of Scx+/Sox9+ cells in the healing process after supraspinatus tendon enthesis injury, comparing the responses of 20- and 3-week-old mice. In the healing process of 20-week-old mice with disorganized fibrovascular tissue in response to injury, a small number of Scx+/Sox9+ cells transiently appeared from 1 week after injury, but they were rarely seen at 4 weeks after injury. Meanwhile, in 3-week-old mice, a thin layer of fibrocartilaginous tissue with calcification was formed at healing enthesis at 4 weeks after injury. From 1 to 2 weeks after injury, more Scx+/Sox9+ cells, widely distributed at the injured site, were seen compared with the 20-week-old mice. At 4 weeks after injury, these cells were located near the surface of the recreated fibrocartilaginous layer. This spatiotemporal localization pattern of Scx+/Sox9+ cells at the injured enthesis in our 3-week-old mouse model was similar to that in postnatal fibrocartilaginous enthesis formation. These findings indicate that Scx+/Sox9+ cells may have a role as entheseal progenitor-like cells during postnatal maturation of fibrocartilaginous entheses and healing after injury in a manner similar to that seen in embryonic development.
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