Mahy P R, Urist M R
UCLA Bone Research Laboratory 90024.
Clin Orthop Relat Res. 1988 Dec(237):236-44.
The object of this research is to investigate the influence of interleukin-1 (IL-1) on heterotopic ossification (HO) induced by bone morphogenetic protein (BMP). Adult mice were implanted with doses of 1, 2, 5, and 10 mg of BMP. Several local injections of 10, 100, and 1000 units of a recombinant IL-1 beta (rIL-1 beta) were administered during the morphogenetic phase of development, starting a day before operation until one week postoperation. While IL-1 acts principally on cell proliferation, BMP primarily shows cell differentiation in the form of HO. BMP-induced HO is quantitated by computer X-ray image scanning, bone ash weight, alkaline phosphatase activity, and histological methods. The area of human BMP-induced HO was completely abolished by injections of polyclonal and monoclonal anti-IL-1 antibody. Monoclonal antibody did not cross-react with the same efficiency as polyclonal with bovine BMP. Polyclonal anti-IL-1 antibody totally neutralizes bovine BMP activity. IL-1-enhanced BMP induced HO and increased the volume of new bone in a statistically significant increment.
本研究的目的是调查白细胞介素-1(IL-1)对骨形态发生蛋白(BMP)诱导的异位骨化(HO)的影响。给成年小鼠植入1、2、5和10毫克剂量的BMP。在发育的形态发生阶段,从手术前一天开始直到术后一周,进行几次局部注射10、100和1000单位的重组IL-1β(rIL-1β)。虽然IL-1主要作用于细胞增殖,但BMP主要以HO的形式表现出细胞分化。通过计算机X射线图像扫描、骨灰重量、碱性磷酸酶活性和组织学方法对BMP诱导的HO进行定量。注射多克隆和单克隆抗IL-1抗体可完全消除人BMP诱导的HO区域。单克隆抗体与牛BMP的交叉反应效率与多克隆抗体不同。多克隆抗IL-1抗体完全中和牛BMP活性。IL-1增强了BMP诱导的HO,并使新骨体积在统计学上有显著增加。