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Role of Mesenchymal Stem Cells in Bone Healing of Rat Bisphosphonate-induced Osteonecrosis of the Jaw

机译:间充质干细胞在大鼠双膦酸盐诱导的颌骨坏死的骨愈合中的作用

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Background and Objective: Bisphosphonates (BPs) have become the primary class of drugs prescribed for the management of bone pathologies associated with excessive bone resorption. Their use has been associated with significant side effect, Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ). The conventional non-surgical and surgical approaches in several BRONJ lesions are sometimes insufficient, therefore, alternative therapies that are safe and that enhance the osteogenesis and angiogenesis are needed. Mesenchymal stem cells (MSCs) have great potential for clinical therapy and have many applications in various fields of regenerative medicine. This study was conducted to evaluate the effect of MSCs on the healing (regenerative) potentials of the bone in bisphosphonate-induced osteonecrotic teeth socket. Materials and Methods: To generate BRONJ-like model, twenty-four adult male rats were received zoledronic acid (Zometa, 0.1 g kg?1 b.wt., twice per week) and dexamethasone (5 mg kg?1 b. wt., once in week) intraperitoneally. At 4 weeks after drugs injection, unilateral left mandibular first molar was extracted and at 3 weeks after teeth extraction, rats were divided randomly into two groups; MSCs group (treated by MSCs topical application) and control group (left without treatment). After euthanization, the mandible of all rats were dissected out and prepared for histopathological examination using H and E staining, Masson trichome as well as immunostaininig with osteopontin. Results: Signs of bone healing and regeneration were significantly detected in osteonecrotic teeth sockets which were treated with topical application of MSCs in comparison to control group. Conclusion: MSCs topical treatment approach might help in restoring, maintaining or improving defective tissue functions that have been compromised by BRONJ.
机译:背景与目的:双膦酸盐(BPs)已成为治疗与过度骨吸收相关的骨病理学的主要药物。它们的使用已引起明显的副作用,即双膦酸盐相关的下颌骨坏死(BRONJ)。在一些BRONJ病变中,常规的非手术和手术方法有时是不够的,因此,需要安全且可增强成骨和血管生成的替代疗法。间充质干细胞(MSCs)在临床治疗中具有巨大潜力,并在再生医学的各个领域具有许多应用。进行这项研究以评估MSC对双膦酸盐诱导的骨坏死牙槽中的骨愈合(再生)潜能的影响。材料与方法:为产生BRONJ样模型,将二十四只成年雄性大鼠接受唑来膦酸(Zometa,0.1 g kg ?1 b.wt.,每周两次)和地塞米松(5 mg kg ?1 b。wt。,每周一次)。药物注射后4周,拔除单侧左下颌第一磨牙,拔牙后3周,将大鼠随机分为两组。 MSCs组(通过MSCs局部应用治疗)和对照组(未治疗)。安乐死后,将所有大鼠的下颌骨解剖,并准备使用H和E染色,Masson trichome以及带有骨桥蛋白的免疫染色进行组织病理学检查。结果:与对照组相比,在局部应用MSCs治疗的坏死牙槽中,明显检测到骨愈合和再生的迹象。结论:MSC的局部治疗方法可能有助于恢复,维持或改善已被BRONJ损害的组织缺陷功能。

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