CCR7 depletion alleviates bony growth imbalance following physeal injury in mice
CCR7 depletion alleviates bony growth imbalance following physeal injury in mice
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DOI：
10.1038/s41598-024-75877-1
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发表时间：
2024-10-22
影响因子：
4.6
通讯作者：
Iwasaki，Norimasa
中科院分区：
文献类型：
--
作者：
Kim，WooYoung;Sakai，Yuko;Iwasaki，Norimasa
生长板是儿童骨骼损伤的常见部位，导致骨骼生长不平衡。趋化因子，包括受体CCR 7，在干细胞募集和软骨稳态中起着至关重要的作用，先前的研究将CCR 7与骨关节炎进展联系起来。然而，其在生长板软骨中的作用仍不清楚。我们在小鼠模型中分析了CCR 7在骺板软骨修复过程中的作用。在3周龄的C57 BL/6小鼠（WT）和CCR 7敲除小鼠（CCR 7 −/−）的胫骨近端造成骨骺损伤。肉眼测量胫骨长度，并对骨骺损伤的切片进行组织学和免疫化学分析。用micro-CT测量胫骨生长板高度、骨体积和软骨下区骨密度。收获间充质干细胞（MSC），并使用qRT-PCR分析成骨分化后的基因表达。在术后1、3和5周，CCR 7 −/−小鼠的损伤时间比WT小鼠短。在CCR 7 −/−小鼠中，骨骺桥的骨体积显著低于WT小鼠。相比之下，CCR−/−和WT小鼠之间以及假手术和手术组之间的软骨下区BMD相当。在成骨分化中，CCR 7 −/−小鼠显示成骨标志物如Osterix、Runx 2和X型胶原蛋白的表达显著降低。我们证明了小鼠中CCR 7的缺失抑制了骨骺桥的形成，并改善了骨骺损伤后的生长失衡。
Growth plates are the frequent sites of skeletal injury in children, leading to skeletal growth imbalances. Chemokines, including the receptor CCR7, play a crucial role in stem cell recruitment and cartilage homeostasis, with previous studies linking CCR7 to osteoarthritis progression. However, its role in growth plate cartilage remains unclear. We analyzed the role of CCR7 in the physeal cartilage repair process in mice model. Physeal injury was created in the proximal tibia in 3-week-old C57BL/6 mice (WT) and CCR7-knockout mice (CCR7−/−). Tibial length was measured macroscopically and sections of the physeal injury were analyzed histologically and immunohistochemically. Height and bone volume of the tibial growth plate and bone mineral density (BMD) of the subchondral area were measured by micro-CT. Mesenchymal stem cells (MSCs) were harvested and gene expression after osteogenic differentiation was analyzed using qRT-PCR. At 1, 3 and 5 weeks postoperatively, injured tibiae of CCR7−/− mice were less shortened than those of WT mice. Bone volume of the physeal bridge was significantly lower in CCR7−/− mice than in WT mice. In contrast, BMD of the subchondral area was comparable between CCR−/− and WT mice, and between sham and operated tibiae. In osteogenic differentiation, CCR7−/− mice showed significantly lowered expression of osteogenic markers such as Osterix, Runx2 and Type X collagen. We demonstrated CCR7 depletion in mice inhibited physeal bridge formation and ameliorated growth imbalances after physeal injury.