Gong Lei, Zhao Yan, Zhang Yi, Ruan Zhi
Department of Emergency, Xinjiang Provincial Corps Hospital, Chinese People's Armed Police Forces, Urumqi
Department of Emergency, Xinjiang Provincial Corps Hospital, Chinese People's Armed Police Forces, Urumqi.
Ann Clin Lab Sci. 2016 Winter;46(1):65-71.
Bone repair is a complex yet highly organized process involving interactions between various cell types and the extracellular environment. Macrophages are not only activated in inflammation during early phases of repair processes, but they are also present in bone throughout the whole bone repair process. Bone marrow derived mesenchymal stem cells (MSCs) represent an attractive therapeutic for bone fracture with their expansion potential, osteogenic capability, and potential for injury. However, less is known about the interaction between macrophage and MSC during bone repair and regeneration. This study was aimed to investigate whether macrophages in different statuses can regulate MSC osteoblast differentiation in vitro. Using in vitro cell coculture of macrophage and MSC, it was shown that macrophage polarization can regulate MSC osteoblast differentiation. This was evidenced by increased alkaline phosphatase (ALP), osteogenic markers, and bone mineralization in M2 macrophage cocultured MSC but decreased in M1 counterpart. These results might be mediated by pro-regenerative cytokines, such as TGF-β, VEGF, and IFG-1, produced by M2 macrophages and detrimental inflammation cytokines, such as IL-6, IL-12, and TNF-α, produced by M1 macrophages. Taken together, this shows that macrophage polarization could be crucial for maintaining bone homeostasis and promoting bone repair by regulating the MSC osteoblast differentiation.
骨修复是一个复杂但高度有序的过程，涉及多种细胞类型与细胞外环境之间的相互作用。巨噬细胞不仅在修复过程早期的炎症中被激活，而且在整个骨修复过程中都存在于骨组织中。骨髓间充质干细胞（MSCs）凭借其增殖潜能、成骨能力和损伤修复潜力，成为治疗骨折颇具吸引力的手段。然而，关于巨噬细胞与MSCs在骨修复和再生过程中的相互作用，人们了解较少。本研究旨在探究不同状态的巨噬细胞在体外是否能够调节MSCs向成骨细胞的分化。通过巨噬细胞与MSCs的体外细胞共培养实验发现，巨噬细胞极化能够调节MSCs向成骨细胞的分化。这一现象在与M2巨噬细胞共培养的MSCs中表现为碱性磷酸酶（ALP）、成骨标志物增加以及骨矿化增强，而在与M1巨噬细胞共培养的MSCs中则相反。这些结果可能是由M2巨噬细胞产生的促再生细胞因子，如转化生长因子-β（TGF-β）、血管内皮生长因子（VEGF）和胰岛素样生长因子-1（IFG-1），以及M1巨噬细胞产生的有害炎症细胞因子，如白细胞介素-6（IL-6）、白细胞介素-12（IL-12）和肿瘤坏死因子-α（TNF-α）介导的。综上所述，这表明巨噬细胞极化对于维持骨稳态以及通过调节MSCs向成骨细胞分化来促进骨修复可能至关重要。
