Development of a murine model of ischemic osteonecrosis to study the effects of aging on bone repair
Development of a murine model of ischemic osteonecrosis to study the effects of aging on bone repair
复制标题
开发缺血性骨坏死小鼠模型以研究衰老对骨修复的影响
DOI：
10.1002/jor.25006
复制
发表时间：
2021
影响因子：
2.8
通讯作者：
Kim Harry K. W.
中科院分区：
文献类型：
--
作者：
Yamaguchi Ryosuke;Kamiya Nobuhiro;Kuroyanagi Gen;Ren Yinshi;Kim Harry K. W.
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，目前还没有成熟的动物模型来研究年龄对缺血性ON后修复过程的影响。本研究的目的是进一步发展缺血性ON的小鼠模型，使用四个年龄组的小鼠来确定年龄对缺血性ON后血管重建和骨修复的影响。小鼠;幼年（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周对小鼠实施安乐死，以评价ON、血运重建和骨修复的程度。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色显示，缺血手术后2天，所有4个年龄组的骨骺中均出现广泛的细胞死亡。在4周时，与成年和中年小鼠相比，幼年小鼠和青春期小鼠的坏死骨髓空间的血运重建和修复显著更大，成骨细胞和破骨细胞数量增加，骨形成率增加。缺血性ON后，与成年小鼠相比，未成熟小鼠的血运重建和骨愈合速度更快，这一结果与缺血性ON后骨修复老化的临床观察结果相似。该小鼠模型可作为一种有用的工具，用于研究青少年和成人ON中与年龄相关的骨修复损伤机制，并开发新的治疗策略。
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.