Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Global Station for Soft Matter, Global Institution for Collaborative Research and Education (GSS, GI-CoRE), Hokkaido University, Sapporo, Japan.
Sci Rep. 2019 Mar 26;9(1):5165. doi: 10.1038/s41598-019-41621-3.
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.
青少年组织的愈合能力具有广泛的无疤痕愈合能力，这与成人愈合反应的疤痕形成过程明显不同。虽然在青少年愈合过程中可以发现许多生长因子，但青少年组织愈合的分子机制仍知之甚少。在这里，我们发现缺乏趋化因子受体 CCR7 的幼年小鼠表现出大规模愈合能力的降低，而 CCR7 耗尽的成年小鼠经历与野生型小鼠相似的正常疤痕形成愈合。此外，CCR7 配体 CCL21 在幼年小鼠受损软骨周围短暂表达，而在成年小鼠中很少表达。值得注意的是，外源性 CCL21 给药可降低成年鼠的疤痕形成愈合，并增强兔骨软骨缺损中的透明软骨修复。我们的数据表明，CCL21/CCR7 轴可能在青少年软骨修复的分子调控机制中发挥作用，这增加了体内调节 CCL21 产生的药物可改善成年患者软骨修复质量的可能性。这种策略可以通过模拟青少年个体的自我修复来预防创伤后关节炎。
