Action of IL-1beta during fracture healing.
Action of IL-1beta during fracture healing.
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DOI：
10.1002/jor.21061
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发表时间：
2010-06
影响因子：
2.8
通讯作者：
Marcucio, Ralph S.
中科院分区：
文献类型：
--
作者：
Lange, Jeffrey;Sapozhnikova, Anna;Lu, Chuanyong;Hu, Diane;Li, Xin;Miclau, Theodore, III;Marcucio, Ralph S.
关键词：
骨损伤后，发育过程，如软骨内骨化和膜内骨化是重演的骨骼再生。与发育相反，骨骼愈合涉及炎症。在愈合的早期阶段，各种炎性细胞浸润受伤部位，清创伤口，并刺激修复过程。对骨修复过程中的炎症过程知之甚少。在这项工作中，我们研究了促炎细胞因子白细胞介素1 β（IL-1 β）对成骨细胞和干细胞分化以及膜内和软骨内骨化的影响，因为IL-1 β对骨骼稳态有影响，并在骨折时上调。我们确定IL-1 β刺激成骨细胞增殖和矿化骨基质的产生，但抑制骨髓源性MSC的增殖和分化。我们接下来进行了功能丧失和获得实验，以确定改变IL-1 β信号传导是否影响骨折愈合。我们没有检测到缺乏IL-1 β受体的小鼠与野生型动物在非稳定或稳定骨折愈合过程中骨痂、软骨和骨基质产生的任何差异。我们观察到在修复的早期阶段给予IL-1 β后愈合过程中的细微变化。在损伤后第10天，软骨与骨痂的比例增加，到第14天，软骨与总骨痂和骨的比例减少。这些变化可能反映了软骨内骨化的轻微加速，或对软骨和骨形成的直接影响。
After bone injury, developmental processes such as endochondral and intramembranous ossification are recapitulated as the skeleton regenerates. In contrast to development, skeletal healing involves inflammation. During the early stages of healing a variety of inflammatory cells infiltrate the injured site, debride the wound, and stimulate the repair process. Little is known about the inflammatory process during bone repair. In this work, we examined the effect of a pro-inflammatory cytokine, Interleukin 1beta (IL-1β), on osteoblast and stem cell differentiation and on intramembranous and endochondral ossification, because IL-1β exerts effects on skeletal homeostasis and is upregulated in response to fracture. We determined that IL-1β stimulated proliferation of osteoblasts and production of mineralized bone matrix, but suppressed proliferation and inhibited differentiation of bone marrow derived MSCs. We next performed loss- and gain-of-function experiments to determine if altering IL-1β signaling affects fracture healing. We did not detect any differences in callus, cartilage, and bone matrix production during healing of non-stabilized or stabilized fractures in mice that lacked the IL-1β receptor compared to wild type animals. We observed subtle alterations in the healing process after administering IL-1β during the early phases of repair. At day 10 after injury, the ratio of cartilage to callus was increased, and by day 14, the proportion of cartilage to total callus and to bone was reduced. These changes could reflect a slight acceleration of endochondral ossification, or direct effects on cartilage and bone formation.
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