Diabetic conditions alter immune cells and are partially responsible for a delayed fracture healing

Objectives: The overall immunogenic state and the cytokine secretion of immune cells after fracture are proposed to have a large impact on the start and process of the fracture healing process. Aim of this study was to investigate if an altered immune status of type 2 diabetics has a direct impact on impaired fracture and wound healing.

Methods:

Blood of diabetic and control patients was taken prior to surgery, serum isolated and cytokine levels analyzed by cytokine array. Differentiation of primary human osteoblasts (phOBs) was analyzed in response to the serum and identified cytokines. Moreover, we developed a model system based on immune cells (THP-1 cells) and osteogenic cells/phOBs. Immune cells were exposed to diabetic conditions and osteogenic differentiation of phOBs was investigated.

Results:

Diabetic patients showed altered serum cytokine levels prior to hip replacement surgery (increased TGF-β, less chemokines). This serum of diabetic patients was found to delay the differentiation of phOBs. Within our model system immune cell conditioned medium itself improved the osteogenic differentiation (1.5 fold increased AP-activity and matrix mineralization) but exposure of immune cells to diabetic conditions before was sufficient to disrupt this positive effect. Further analysis of the conditioned medium revealed 10-fold increased IL-1β secretion in response to insulin and doubled secretion of TNF-α. Following, migration of osteogenic cells to the conditioned medium was reduced with applied diabetic conditions before (2-fold, p = 0.0315).

Conclusions:

Our results show that the altered immune status of diabetics could be a major reason for the impaired fracture healing of diabetics.