Ballout Nissrine, Toumieux Sylvestre, Darwiche Walaa, Gomila Cathy, Trécherel Eric, Accadbled Franck, Laurencin-Dalicieux Sara, Gennero Isabelle, Kovensky José, Boullier Agnès, Ausseil Jérôme
Société d'Accélération du Transfert de Technologie-Nord, F-59800 Lille, France.
Institut Toulousain des Maladies Infectieuses et Inflammatoires, INSERM UMR1291, CNRS UMR5051, University of Toulouse, F-31024 Toulouse, France.
Pharmaceuticals (Basel). 2025 Feb 5;18(2):215. doi: 10.3390/ph18020215.
: Delays in bone healing and complications of remodeling constitute a major medical problem-particularly in older adults and patients with comorbidities. Current therapeutic approaches are based on strategies that promote bone regeneration. We recently identified a disaccharide compound (DP2) that enhances in vitro mineralization in human osteoblast cells via the early activation of Runx2 and the induction of osteoblast differentiation. : First, a calcium quantification assay was performed to assess mineralization in MC3T3-E1 cells. Next, microcomputed tomography and histological analyses were used to examine in vivo bone repair in a rat 5 mm cranial defect model following the implantation of DP2 coupled to a micro/macroporous biphasic CaP ceramic (MBCP) or collagen scaffold. : Here, we demonstrated that DP2 induced osteogenic differentiation and significantly elevated calcium matrix deposition in the murine preosteoblast cell line MC3T3-E1. We found that treatment with DP2 coupled to MBCP repaired the calvarial defect on post-implantation day 91. It significantly increased bone mineral density starting on day 29 post-treatment. In addition, DP2 did not induce ectopic bone formation. : Taken as a whole, these results show that DP2 is a promising candidate treatment for delayed bone healing.
骨愈合延迟和重塑并发症是一个主要的医学问题,尤其是在老年人和患有合并症的患者中。目前的治疗方法基于促进骨再生的策略。我们最近发现了一种二糖化合物(DP2),它通过早期激活Runx2和诱导成骨细胞分化来增强人成骨细胞的体外矿化。首先,进行钙定量测定以评估MC3T3-E1细胞中的矿化。接下来,在植入与微/大孔双相磷酸钙陶瓷(MBCP)或胶原蛋白支架偶联的DP2后,使用微型计算机断层扫描和组织学分析来检查大鼠5毫米颅骨缺损模型中的体内骨修复情况。在这里,我们证明DP2诱导了成骨分化,并显著提高了小鼠前成骨细胞系MC3T3-E1中的钙基质沉积。我们发现,在植入后第91天,用与MBCP偶联的DP2治疗修复了颅骨缺损。从治疗后第29天开始,它显著增加了骨矿物质密度。此外,DP2没有诱导异位骨形成。总体而言,这些结果表明DP2是治疗骨愈合延迟的一个有前景的候选药物。