Takayama Tadahiro, Dai Jisen, Tachi Keita, Shohara Ryutaro, Kasai Hironori, Imamura Kentaro, Yamano Seiichi
1 Department of Periodontology, Nihon University School of Dentistry, Tokyo, Japan.
2 Division of Advanced Dental Treatment, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan.
J Biomater Appl. 2017 Feb;31(7):1049-1061. doi: 10.1177/0885328216686727. Epub 2017 Jan 5.
Stromal cell-derived factor-1 (SDF-1) is a cytokine that is important in stem and progenitor cell recruitment in tissue repair after injury. Regenerative procedures using collagen membranes (CMs) are presently well established in periodontal and implant dentistry. The objective of this study is to test the subsequent effects of the released SDF-1 from a CM on bone regeneration compared to platelet-derived growth factor (PDGF) in vitro and in vivo. For in vitro studies, cell proliferation, alkaline phosphatase activity, and osteoblastic differentiation marker genes were assessed after MC3T3-E1 mouse preosteoblasts were cultured with CMs containing factors. In vivo effects were investigated by placement of CMs containing SDF-1 or PDGF using a rat mandibular bone defect model. At 4 weeks after the surgery, the new bone formation was measured using micro-computed tomography (µCT) and histological analysis. The results of in vitro studies revealed that CM delivery of SDF-1 significantly induced cell proliferation, ALP activity, and gene expression of all osteogenic markers compared to the CM alone or control, similar to PDGF. Quantitative and qualitative µCT analysis for volume of new bone formation and the percentage of new bone area showed that SDF-1-treated groups significantly increased and accelerated bone regeneration compared to control and CM alone. The enhancement of bone formation in SDF-1-treated animals was dose-dependent and with levels similar to those measured with PDGF. These results suggest that a CM with SDF-1 may be a great candidate for growth factor delivery that could be a substitute for PDGF in clinical procedures where bone regeneration is necessary.
基质细胞衍生因子-1(SDF-1)是一种细胞因子,在损伤后组织修复过程中对干细胞和祖细胞的募集起着重要作用。目前,使用胶原膜(CMs)的再生程序在牙周病学和种植牙科中已得到充分确立。本研究的目的是在体外和体内测试与血小板衍生生长因子(PDGF)相比,CM释放的SDF-1对骨再生的后续影响。对于体外研究,在MC3T3-E1小鼠前成骨细胞与含有因子的CMs共培养后,评估细胞增殖、碱性磷酸酶活性和成骨细胞分化标记基因。使用大鼠下颌骨缺损模型,通过植入含有SDF-1或PDGF的CMs来研究体内效应。术后4周,使用微型计算机断层扫描(µCT)和组织学分析测量新骨形成情况。体外研究结果显示,与单独的CM或对照组相比,CM递送SDF-1显著诱导了细胞增殖、碱性磷酸酶活性以及所有成骨标记物的基因表达,与PDGF相似。对新骨形成体积和新骨面积百分比的定量和定性µCT分析表明,与对照组和单独的CM相比,SDF-1处理组显著增加并加速了骨再生。SDF-1处理动物的骨形成增强呈剂量依赖性,且水平与用PDGF测量的水平相似。这些结果表明,含有SDF-1的CM可能是生长因子递送的理想候选物,在需要骨再生的临床程序中可替代PDGF。