CCL21/CCR7 axis regulating juvenile cartilage repair can enhance cartilage healing in adults
CCL21/CCR7 axis regulating juvenile cartilage repair can enhance cartilage healing in adults
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DOI：
10.1038/s41598-019-41621-3
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发表时间：
2019-03-26
影响因子：
4.6
通讯作者：
Iwasaki, Norimasa
中科院分区：
文献类型：
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作者：
Joutoku, Zenta;Onodera, Tomohiro;Iwasaki, Norimasa
幼年组织愈合能够进行广泛的无瘢痕愈合，这与成年愈合反应的瘢痕形成过程不同。虽然许多生长因子可以发现在幼年愈合过程中，幼年组织愈合的分子机制知之甚少。在这里，我们表明，缺乏趋化因子受体CCR 7的幼年小鼠表现出减少的大规模愈合潜力，而CCR 7耗尽的成年小鼠进行正常的瘢痕形成愈合类似于野生型小鼠。此外，CCR 7配体CCL 21在幼年小鼠受损软骨周围瞬时表达，而在成年小鼠中很少表达。值得注意的是，在兔骨软骨缺损中，对成人施用外源性CCL 21减少了瘢痕形成愈合并增强了透明软骨修复。我们的数据表明，CCL 21/CCR 7轴可能在青少年软骨修复的分子控制机制中发挥作用，提高了体内调节CCL 21产生的药物可以改善成人软骨修复质量的可能性。这种策略可以通过模仿青少年个体的自我修复来预防创伤后关节炎。
Juvenile tissue healing is capable of extensive scarless healing that is distinct from the scar-forming process of the adult healing response. Although many growth factors can be found in the juvenile healing process, the molecular mechanisms of juvenile tissue healing are poorly understood. Here we show that juvenile mice deficient in the chemokine receptor CCR7 exhibit diminished large-scale healing potential, whereas CCR7-depleted adult mice undergo normal scar-forming healing similar to wild type mice. In addition, the CCR7 ligand CCL21 was transiently expressed around damaged cartilage in juvenile mice, whereas it is rarely expressed in adults. Notably, exogenous CCL21 administration to adults decreased scar-forming healing and enhanced hyaline-cartilage repair in rabbit osteochondral defects. Our data indicate that the CCL21/CCR7 axis may play a role in the molecular control mechanism of juvenile cartilage repair, raising the possibility that agents modulating the production of CCL21 in vivo can improve the quality of cartilage repair in adults. Such a strategy may prevent post-traumatic arthritis by mimicking the self-repair in juvenile individuals.