PDF(Pubmed)
Abstract：
Diabetes mellitus is a main risk factor for delayed fracture healing and fracture non-unions. Successful fracture healing requires stimuli from different immune cells, known to be affected in diabetics. Especially, application of mononuclear cells has been proposed to promote wound and fracture healing. Thus, aim was to investigate the effect of pre-/diabetic conditions on mononuclear cell functions essential to promote osteoprogenitor cell function. We here show that pre-/diabetic conditions suppress the expression of chemokines, e.g., CCL2 and CCL8 in osteoprogenitor cells. The associated MCP-1 and MCP-2 were significantly reduced in serum of diabetics. Both MCPs chemoattract mononuclear THP-1 cells. Migration of these cells is suppressed under hyperglycemic conditions, proposing that less mononuclear cells invade the site of fracture in diabetics. Further, we show that the composition of cytokines secreted by mononuclear cells strongly differ between diabetics and controls. Similar is seen in THP-1 cells cultured under hyperinsulinemia or hyperglycemia. The altered secretome reduces the positive effect of the THP-1 cell conditioned medium on migration of osteoprogenitor cells. In summary, our data support that factors secreted by mononuclear cells may support fracture healing by promoting migration of osteoprogenitor cells but suggest that this effect might be reduced in diabetics.
摘要：
糖尿病是骨折愈合延迟和骨折不愈合的主要危险因素。成功的骨折愈合需要来自不同免疫细胞的刺激,已知在糖尿病患者中受到影响。尤其是,已提出应用单核细胞促进伤口和骨折愈合。因此，目的是研究糖尿病前期/糖尿病对促进骨祖细胞功能所必需的单核细胞功能的影响。我们在这里显示，前/糖尿病的条件抑制趋化因子的表达，例如，骨祖细胞中的CCL2和CCL8。糖尿病患者血清中相关的MCP-1和MCP-2显著降低。两种MCP化学吸引单核THP-1细胞。这些细胞的迁移在高血糖条件下被抑制，提出糖尿病患者中侵入骨折部位的单核细胞较少。Further,我们显示，糖尿病患者和对照组的单核细胞分泌的细胞因子组成存在很大差异。在高胰岛素血症或高血糖下培养的THP-1细胞中观察到类似的情况。改变的分泌组降低了THP-1细胞条件培养基对骨祖细胞迁移的积极作用。总之,我们的数据支持单核细胞分泌的因子可能通过促进骨祖细胞的迁移来支持骨折愈合,但提示糖尿病患者的这种作用可能会降低.
