The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, 430079, People's Republic of China.
Department of Dental Implantology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, 430079, People's Republic of China.
J Biomed Mater Res A. 2018 May;106(5):1236-1246. doi: 10.1002/jbm.a.36321. Epub 2018 Jan 23.
Bone grafts are widely used in bone regeneration to increase the speed and quality of new bone formation. While they are routinely characterized based on their biocompatible and bioactive properties, they also exert a profound impact on host immune responses, which in turn can display a significant effect on the healing and repair process. In this study, we investigated the role of macrophage behavior on deproteinized bovine bone matrix (DBBM, BioOss) to investigate their impact on creating either a pro- or anti-inflammatory microenvironment for tissue integration. RT-PCR and immunofluorescence staining results demonstrated the ability for RAW 264.7 cells to polarize toward M2 wound-healing macrophages in response to DBBM and positive control (IL-4). Interestingly, significantly higher expression of interleukin-10 and higher number of multinucleated giant cells (MNGCs) was observed in the DBBM group. Thereafter, conditioned media (CM) from macrophages cultured with DBBM seeded with MC3T3-E1 cells demonstrated a marked increase in osteoblast differentiation. Noteworthy, this effect was reversed by blocking IL10 with addition of IL10 antibody to CM from the DBBM macrophages. Furthermore, the use of dendritic cell specific transmembrane protein (DC-STAMP)-knockout to inhibit MNGC formation in the DBBM group resulted in a significant reduction in osteoblast differentiation, indication a pivotal role for MNGCs in biomaterials-induced osteogenesis. The results from this study indicate convincingly that the immune response of macrophages towards DBBM has a potent effect on osteoblast differentiation. Furthermore, DBBM promoted macrophage fusion and polarization towards an M2 wound-healing phenotype, further created a microenvironment favoring biomaterial-induced osteogenesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1236-1246, 2018.
骨移植物广泛用于骨再生以增加新骨形成的速度和质量。虽然它们通常根据其生物相容性和生物活性特性进行表征，但它们也对宿主免疫反应产生深远影响，这反过来又对愈合和修复过程产生重大影响。在这项研究中，我们研究了巨噬细胞行为对脱蛋白牛骨基质（DBBM，BioOss）的作用，以研究它们对创建有利于组织整合的促炎或抗炎微环境的影响。RT-PCR 和免疫荧光染色结果表明 RAW 264.7 细胞能够向 DBBM 和阳性对照（IL-4）响应极化成 M2 伤口愈合巨噬细胞。有趣的是，在 DBBM 组中观察到白细胞介素-10 的表达显著增加，多核巨细胞（MNGCs）的数量也显著增加。此后，用 DBBM 培养的巨噬细胞的条件培养基（CM）在 MC3T3-E1 细胞上接种后显示出成骨细胞分化的明显增加。值得注意的是，通过向 DBBM 巨噬细胞的 CM 添加 IL10 抗体阻断 IL10，这种作用被逆转。此外，使用树突状细胞特异性跨膜蛋白（DC-STAMP）敲除抑制 DBBM 组中的 MNGC 形成导致成骨细胞分化的显著减少，表明 MNGC 在生物材料诱导的成骨作用中起关键作用。这项研究的结果令人信服地表明，巨噬细胞对 DBBM 的免疫反应对成骨细胞分化有强烈影响。此外，DBBM 促进巨噬细胞融合和极化为 M2 伤口愈合表型，进一步创造了有利于生物材料诱导成骨的微环境。© 2018 Wiley Periodicals，Inc. J Biomed Mater Res Part A：106A：1236-1246，2018。
