ERK5在小鼠骨质疏松性骨折愈合过程中作用的实验研究
Study of ERK5 in the healing process of osteoporotic fracture in mice
  
DOI:10.3969/j.issn.1006.7108.2018.07.003
中文关键词:  ERK5  骨质疏松  骨折  成骨相关蛋白  动物实验
英文关键词:ERK5  Osteoporosis  Fracture  Osteogenesis-related protein  Animal experimentation
基金项目:国家自然科学基金(81672207);兰州大学第二医院博士科研基金(ynbskyjj2015-2-9)
作者单位
盛晓赟1 郭来威1,2 闫亮2 万浪2 姜金1 夏亚一1,2* 1.兰州大学第二医院关节外科,甘肃 兰州 730000 2.甘肃省骨关节疾病研究重点实验室,甘肃 兰州 730000 
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中文摘要:
      目的 通过构建小鼠骨质疏松骨折模型,研究ERK5在骨质疏松性骨折愈合过程中的作用。方法 将108只6周龄雌性昆明小鼠随机分成4组,通过手术切除小鼠双侧卵巢及小鼠股骨离断分别构建骨质疏松(OVX)和骨折模型(Fracture),然后给实验组小鼠每日腹腔注射ERK5特异性阻断剂XMD8-92,于1 w、2 w、4 w后分别处死一定数量的小鼠,取术侧股骨标本,行X线片检查、股骨骨痂Micro-CT、HE染色及免疫组织化学染色检查,观察骨折端骨小梁生长情况,骨痂内成骨相关蛋白及ERK5表达情况。结果 给予实验小鼠注射XMD8-92后第2周及第4周,Fracture组小鼠骨痂生长较快,骨小梁数目较多,厚度较大,成骨相关蛋白ALP、Runx2的表达相对较多(P<0.05),而Fracture+XMD8-92组小鼠骨痂生长则相对缓慢,骨小梁稀少且绯薄,结构相对较乱,碱性磷酸酶(alkaline phosphatase,ALP)、Runx2表达较少(P<0.05);且OVX+Fracture+XMD8-92组小鼠与OVX+Fracture组小鼠相比,骨小梁生成更少且紊乱,骨痂生长明显延迟,ALP、Runx2表达量显著减少(P<0.05)。结论 ERK5影响骨折端骨痂形成的速度和质量,在促进骨质疏松性骨折愈合过程中起着十分重要的生理作用。
英文摘要:
      Objective To study the role of ERK5 in the healing process of osteoporotic fractures by establishing osteoporotic fracture model in mice. Methods 108 6-week-old female mice were randomly divided into 4 groups. Osteoporosis and fracture models were established by surgically resecting the bilateral ovaries and cutting off the femur. Then the experimental mice were injected with ERK5-specific blocker XMD8-92 intraperitoneally, and a certain number of mice were sacrificed at the 1st, 2nd and 4th week. X-ray examination, Micro-CT, HE staining and immunohistochemically staining of bone callus were performed to observe the growth of trabecular bone, and the expression of osteogenesis-related proteins and ERK5. Results The experimental mice were injected with XMD8-92 at the 2nd week and the 4th week. In the fracture group, the callus of mice grew faster, there were more and thicker trabecular bone, and the expression of the osteogenesis-related proteins ALP and Runx-2 was higher (P<0.05). The callus grew much slower with less and thinner trabecular bone, and the expression of the osteogenesis-related proteins ALP and Runx-2 was lower in the fracture+XMD8-92 group (P<0.05). Compared with the osteoporotic fracture group, the osteoporotic fracture + XMD8-92 group showed less and more disordered trabecular bone formation, significant delay in the growth of callus, and significantly lower ALP and Runx-2 expression (P<0.05). Conclusion ERK5 affects the rate and quality of callus formation in the area of fracture and plays an important physiological role in the process of osteoporotic fracture healing.
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