Center for Excellence in Hip, Scottish Rite for Children, Dallas, Texas, USA.
Department of Orthopaedic Surgery, Guraduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Orthop Res. 2021 Dec;39(12):2663-2670. doi: 10.1002/jor.25006. Epub 2021 Mar 18.
Age at onset is one of the most important predictors of outcome following ischemic osteonecrosis (ON). Currently, there is no well-established animal model to study the effects of age on the repair process following ischemic ON. The purpose of this study was to further advance a murine model of ischemic ON using four age groups of mice to determine the effects of aging on revascularization and bone repair following ischemic ON. Ischemia was surgically induced in the distal femoral epiphysis of four age groups of skeletally immature and mature mice; juvenile (5 weeks), adolescent (12 weeks), adult (22 weeks), and middle age (52 weeks). Mice were euthanized at 2 days or 4 weeks post-ischemia surgery to evaluate the extent of ON, revascularization, and bone repair. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining showed extensive cell death in the epiphysis of all four age groups at 2 days post-ischemia surgery. At 4 weeks, the juvenile mice followed by the adolescent mice had significantly greater revascularization and repair of the necrotic marrow space, increased osteoblast and osteoclast numbers, and increased bone formation rates compared to the adult and middle-age mice. Faster revascularization and bone healing were observed in the skeletally immature mice compared to the skeletally mature mice following ischemic ON. The findings resemble the clinical observation of aging on bone repair following ischemic ON. The mouse model may serve as a useful tool to investigate the mechanisms underlying the age-related impairment of bone repair in adolescent and adult ON and to develop novel therapeutic strategies.
发病年龄是缺血性骨坏死（ON）预后的最重要预测因素之一。目前，尚无成熟的动物模型来研究年龄对缺血性 ON 修复过程的影响。本研究旨在进一步推进使用四个年龄组的小鼠建立缺血性 ON 的动物模型，以确定年龄对缺血性 ON 后再血管化和骨修复的影响。通过手术在未成年和成年小鼠的股骨远端骨骺诱导缺血；幼鼠（5 周）、青少年（12 周）、成年（22 周）和中年（52 周）。在缺血手术后 2 天或 4 周处死小鼠，以评估 ON、再血管化和骨修复的程度。末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记染色显示，在缺血手术后 2 天，四个年龄组的骨骺中均有广泛的细胞死亡。在 4 周时，与成年和中年小鼠相比，幼年小鼠和青少年小鼠的再血管化和坏死骨髓空间修复明显更多，破骨细胞和成骨细胞数量增加，骨形成率增加。与成年和中年小鼠相比，在缺血性 ON 后，未成年小鼠的再血管化和骨愈合更快。这些发现类似于临床观察到的年龄对缺血性 ON 后骨修复的影响。该小鼠模型可能成为研究青少年和成年 ON 中与年龄相关的骨修复受损的机制以及开发新的治疗策略的有用工具。
