Fukusato Shin, Nagao Masashi, Fujihara Kei, Yoneda Taiju, Arai Kiyotaka, Koch Manuel, Kaneko Kazuo, Ishijima Muneaki, Izu Yayoi
Department of Medicine for Orthopaedics and Motor Organs, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
Medical Technology Innovation Center, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
J Clin Med. 2021 Sep 7;10(18):4051. doi: 10.3390/jcm10184051.
Anterior cruciate ligament (ACL) rupture is a common knee injury for athletes. Although surgical reconstruction is recommended for the treatment of ACL ruptures, 100% functional recovery is unlikely. Therefore, the discovery of risk factors for ACL ruptures may prevent injury. Several studies have reported an association between polymorphisms of the collagen XII gene and ACL rupture. Collagen XII is highly expressed in tendons and ligaments and regulates tissue structure and mechanical property. Therefore, we hypothesized that collagen XII deficiency may cause ACL injury. To elucidate the influence of collagen XII deficiency on ACL, we analyzed a mouse model deficient for . Four- to 19-week-old male and wild-type control mice were used for gait analysis; histological and immunofluorescent analysis of collagen XII, and real-time RT-PCR evaluation of mRNA expression. The mice showed an abnormal gait with an approximately 2.7-fold increase in step angle, suggesting altered step alignment. mice displayed 20-60% ACL discontinuities, but 0% discontinuity in the posterior cruciate ligament. No discontinuities in knee ligaments were found in wild-type mice. Collagen XII mRNA expression in the ACL tended to decrease with aging. Our study demonstrates for the first time that collagen XII deficiency increases the risk of ACL injury.
前交叉韧带(ACL)断裂是运动员常见的膝关节损伤。尽管建议通过手术重建来治疗ACL断裂,但不太可能实现100%的功能恢复。因此,发现ACL断裂的危险因素可能预防损伤。几项研究报告了胶原蛋白XII基因多态性与ACL断裂之间的关联。胶原蛋白XII在肌腱和韧带中高度表达,并调节组织结构和力学性能。因此,我们推测胶原蛋白XII缺乏可能导致ACL损伤。为了阐明胶原蛋白XII缺乏对ACL的影响,我们分析了一种缺乏胶原蛋白XII的小鼠模型。使用4至19周龄的雄性胶原蛋白XII缺乏小鼠和野生型对照小鼠进行步态分析;对胶原蛋白XII进行组织学和免疫荧光分析,以及对胶原蛋白XII mRNA表达进行实时RT-PCR评估。胶原蛋白XII缺乏小鼠表现出异常步态,步角增加约2.7倍,表明步幅对齐改变。胶原蛋白XII缺乏小鼠的ACL出现20%至60%的连续性中断,但后交叉韧带的连续性中断为0%。野生型小鼠的膝关节韧带未发现连续性中断。ACL中胶原蛋白XII mRNA表达倾向于随年龄增长而降低。我们的研究首次证明胶原蛋白XII缺乏会增加ACL损伤的风险。