Unravelling the Impact of Diabetes on Insulin-like Growth Factor (IGF) Axis Signalling in Mesenchymal Stem Cells Isolated from the Bone of Knee Joints

Diabetes mellitus (T2DM) represents a major health problem with several potentially life-threatening complications including cardiovascular disease and osteopathy. Bone marrow mesenchymal stem cells (BM-MSCs) are a promising candidate for bone regeneration, and the insulin-like growth factor (IGF) axis plays a fundamental role in both bone regeneration and stem cell biology. Still, its expression profile is yet to be assessed in diabetic BM-MSCs. This study investigated IGF axis gene and protein expression in BM-MSCs isolated from the knee joints of diabetic and non-diabetic donors. BM-MSCs were cultured under basal and osteogenic conditions for 1, 2 and 3 weeks. Relative expression levels of the IGF axis genes were assessed using qPCR while protein concentrations of IGFBP-2, -3 and -4 were assessed using ELISA. Diabetic BM-MSCs showed lower mRNA levels of IGF binding proteins (IGFBP)-2, -3 and -4 but both cell populations displayed comparable protein levels. Moreover, the osteogenic cultures of diabetic and non-diabetic BM-MSCs equally demonstrated a trend of IGFBP-2 upregulation along with IGF-1 and IGFBP-5 downregulation. Non-diabetic BM-MSCs showed significant time-dependent increases in IGFBP-3 and -4 concentrations in basal and osteogenic cultures respectively. These molecules could be addressed to improve the regenerative potentials of BM-MSCs particularly under diabetic conditions, and further research is warranted into the possible roles of IGFBPs proteinases and their inhibitors in bone biology.