The inflammatory phase of fracture healing is influenced by oestrogen status in mice.
The inflammatory phase of fracture healing is influenced by oestrogen status in mice.
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DOI：
10.1186/s40001-017-0264-y
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发表时间：
2017-07-06
影响因子：
4.2
通讯作者：
Ignatius A
中科院分区：
文献类型：
--
作者：
Haffner-Luntzer M;Fischer V;Prystaz K;Liedert A;Ignatius A
众所周知，在雌激素缺乏的情况下，绝经后骨质疏松女性的骨折愈合会延迟。为了证实这一点，实验研究表明，卵巢切除动物的骨痂形成受到了损害。众所周知，雌激素缺乏会影响伤口愈合过程中的免疫系统和炎症反应。因为正常的骨愈合需要平衡的免疫反应，所以我们有兴趣确定骨折后的早期免疫反应是否受到雌激素耗竭的影响。为了解决上述问题，雌性小鼠接受了双侧卵巢切除(OVX)或假手术，并在OVX/Sham手术后8周进行股骨截骨。分别于骨折后第1天和第3天用流式细胞仪和免疫组织化学方法检测OVX对骨折愈合过程中免疫细胞和促炎细胞因子表达的影响。骨折后一天，OVX小鼠和假小鼠骨折血肿中的免疫细胞数量和数量没有差异。然而，在骨折后第3天，OVX-小鼠显示出明显更多的中性粒细胞。OVX小鼠骨折后3d骨折骨痂局部雌激素反应性和促炎性细胞因子中期因子(MDK)和白介素6(IL-6)的表达较假手术组增加，提示这两个因素可能参与了中性粒细胞的增加。证实了这一点，MDK抗体治疗减少了OVX小鼠骨折骨痂中的中性粒细胞数量，并减少了局部IL-6的表达。这些数据表明，雌激素缺乏影响骨折后的早期炎症阶段。这可能是雌激素耗尽后延迟骨折愈合的原因之一。
Fracture healing is known to be delayed in postmenopausal, osteoporotic females under oestrogen-deficient conditions. Confirming this, experimental studies demonstrated impaired callus formation in ovariectomised animals. Oestrogen-deficiency is known to affect the immune system and the inflammatory response during wound healing. Because a balanced immune response is required for proper bone healing, we were interested to ascertain whether the early immune response after facture is affected by oestrogen depletion. To address the above question, female mice received either a bilateral ovariectomy (OVX) or were sham-operated, and femur osteotomy was performed 8 weeks after OVX/sham operation. The effects of OVX on the presence of immune cells and pro-inflammatory cytokines were evaluated by flow cytometry and immunohistochemistry of the fracture calli on days 1 and 3 after fracture. One day after fracture, immune cell numbers and populations in the fracture haematoma did not differ between OVX- and sham-mice. However, on day 3 after fracture, OVX-mice displayed significantly greater numbers of neutrophils. Local expression of the oestrogen-responsive and pro-inflammatory cytokine midkine (Mdk) and interleukin-6 (IL-6) expression in the fracture callus were increased in OVX-mice on day 3 after fracture compared with sham-mice, indicating that both factors might be involved in the increased presence of neutrophils. Confirming this, Mdk-antibody treatment decreased the number of neutrophils in the fracture callus and reduced local IL-6 expression in OVX-mice. These data indicate that oestrogen-deficiency influences the early inflammatory phase after fracture. This may contribute to delayed fracture healing after oestrogen depletion.
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影响因子：
2.5
作者：
Ikutomo, Masako;Sakakima, Harutoshi;Yoshida, Yoshihiro
通讯作者：
Yoshida, Yoshihiro
影响因子：
3.7
作者：
Haffner-Luntzer M;Kemmler J;Heidler V;Prystaz K;Schinke T;Amling M;Kovtun A;Rapp AE;Ignatius A;Liedert A
通讯作者：
Liedert A
影响因子：
4.5
作者：
Bastian, Okan W.;Kuijer, Anne;Blokhuis, Taco J.
通讯作者：
Blokhuis, Taco J.
DOI：
10.1097/ta.0b013e3181c4544d
发表时间：
2010-11-01
影响因子：
--
作者：
Beil, Frank Timo;Barvencik, Florian;Amling, Michael
通讯作者：
Amling, Michael
影响因子：
3.1
作者：
Kovtun, A.;Bergdolt, S.;Ignatius, A.
通讯作者：
Ignatius, A.