Ballout Nissrine, Boullier Agnès, Darwiche Walaa, Ait-Mohand Katia, Trécherel Eric, Gallégo Théo, Gomila Cathy, Yaker Linda, Gennero Isabelle, Kovensky José, Ausseil Jérôme, Toumieux Sylvestre
Société d'Accélération du Transfert de Technologie-Nord, 59800 Lille, France.
Institut Toulousain des Maladies Infectieuses et Inflammatoires, INSERM UMR1291, CNRS UMR5051, University of Toulouse III, 31024 Toulouse, France.
Pharmaceuticals (Basel). 2023 Oct 24;16(11):1512. doi: 10.3390/ph16111512.
Bone fracture healing is a complex biological process involving four phases coordinated over time: hematoma formation, granulation tissue formation, bony callus formation, and bone remodelling. Bone fractures represent a significant health problem, particularly among the elderly population and patients with comorbidities. Therapeutic strategies proposed to treat such fractures include the use of autografts, allografts, and tissue engineering strategies. It has been shown that bone morphogenetic protein 2 (BMP-2) has a therapeutic potential to enhance fracture healing. Despite the clinical efficacy of BMP-2 in osteoinduction and bone repair, adverse side effects and complications have been reported. Therefore, in this in vitro study, we propose the use of a disaccharide compound (DP2) to improve the mineralisation process. We first evaluated the effect of DP2 on primary human osteoblasts (HOb), and then investigated the mechanisms involved. Our findings showed that (i) DP2 improved osteoblast differentiation by inducing alkaline phosphatase activity, osteopontin, and osteocalcin expression; (ii) DP2 induced earlier in vitro mineralisation in HOb cells compared to BMP-2 mainly by earlier activation of Runx2; and (iii) DP2 is internalized in HOb cells and activates the protein kinase C signalling pathway. Consequently, DP2 is a potential therapeutical candidate molecule for bone fracture repair.
骨折愈合是一个复杂的生物学过程,涉及随时间协调的四个阶段:血肿形成、肉芽组织形成、骨痂形成和骨重塑。骨折是一个重大的健康问题,尤其在老年人群和患有合并症的患者中。为治疗此类骨折而提出的治疗策略包括使用自体移植物、异体移植物和组织工程策略。研究表明,骨形态发生蛋白2(BMP-2)具有促进骨折愈合的治疗潜力。尽管BMP-2在骨诱导和骨修复方面具有临床疗效,但也有不良副作用和并发症的报道。因此,在这项体外研究中,我们提出使用一种二糖化合物(DP2)来改善矿化过程。我们首先评估了DP2对原代人成骨细胞(HOb)的影响,然后研究了其中涉及的机制。我们的研究结果表明:(i)DP2通过诱导碱性磷酸酶活性、骨桥蛋白和骨钙素表达来改善成骨细胞分化;(ii)与BMP-2相比,DP2主要通过更早激活Runx2在HOb细胞中诱导更早的体外矿化;(iii)DP2被HOb细胞内化并激活蛋白激酶C信号通路。因此,DP2是骨折修复的潜在治疗候选分子。