Vater Corina, Mehnert Elisabeth, Bretschneider Henriette, Bolte Julia, Findeisen Lisa, Matuszewski Lucas-Maximilian, Zwingenberger Stefan
University Center of Orthopedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany.
Center for Translational Bone, Joint and Soft Tissue Research, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Biomedicines. 2021 Nov 18;9(11):1712. doi: 10.3390/biomedicines9111712.
Difficulties in treating pseudarthrosis and critical bone defects are still evident in physicians' clinical routines. Bone morphogenetic protein 2 (BMP-2) has shown promising osteoinductive results but also considerable side effects, not unexpected given that it is a morphogen. Thus, the bone regenerative potential of the novel selective, non-morphogenic EP prostaglandin receptor agonist KMN-159 was investigated in this study. Therefore, mineralized collagen type-1 matrices were loaded with different amounts of BMP-2 or KMN-159 and implanted into a 5 mm critical-sized femoral defect in rats. After 12 weeks of observation, micro-computed tomography scans were performed to analyze the newly formed bone volume (BV) and bone mineral density (BMD). Histological analysis was performed to evaluate the degree of defect healing and the number of vessels, osteoclasts, and osteoblasts. Data were evaluated using Kruskal-Wallis followed by Dunn's post hoc test. As expected, animals treated with BMP-2, the positive control for this model, showed a high amount of newly formed BV as well as bone healing. For KMN-159, a dose-dependent effect on bone regeneration could be observed up to a dose optimum, demonstrating that this non-morphogenic mechanism of action can stimulate bone formation in this model system.
在医生的临床工作中，治疗骨不连和严重骨缺损的困难依然明显。骨形态发生蛋白2（BMP-2）已显示出有前景的骨诱导效果，但也有相当多的副作用，鉴于它是一种形态发生素，出现这样的副作用并不意外。因此，本研究对新型选择性、非形态发生性的EP前列腺素受体激动剂KMN-159的骨再生潜力进行了研究。为此，将不同量的BMP-2或KMN-159加载到矿化的I型胶原基质中，并植入大鼠5毫米临界尺寸的股骨缺损处。观察12周后，进行微型计算机断层扫描以分析新形成的骨体积（BV）和骨矿物质密度（BMD）。进行组织学分析以评估缺损愈合程度以及血管、破骨细胞和成骨细胞的数量。数据采用Kruskal-Wallis检验，随后进行Dunn事后检验进行评估。正如预期的那样，用该模型的阳性对照BMP-2治疗的动物显示出大量新形成的BV以及骨愈合。对于KMN-159，在达到最佳剂量之前可观察到对骨再生的剂量依赖性效应，表明这种非形态发生性作用机制可在该模型系统中刺激骨形成。
