transglutaminase 2 (TGM2) and Its Novel Targeted Activator in Diabetic Bone Regeneration: From Mechanism to Application

To screen and identify key molecule regulating T2DM (Type 2 diabetes mellitus)-impaired bone regeneration, cellular osteogenic potential and mitochondrial function, and to elucidate the regulatory mechanisms of this molecule. Microarray analysis was performed to compare transcriptional profiles between bone marrow mesenchymal stem cells (BMMSCs) derived from normal rats (Wistar) and T2DM rats (GK). BMMSCs were transfected with overexpression plasmids targeting candidate molecule and small interfering RNA (siRNA) was used to silence candidate gene expression, then the osteogenic differentiation potential and mitochondrial function of BMMSCs were assessed. Microarray and qRT-PCR revealed significantly elevated expression of TGM2 in BMMSCs from T2DM rats compared to those from normal rats. TGM2 silencing suppressed osteogenic differentiation and mitochondrial function of BMMSCs, and TGM2 overexpression rescued osteogenic capacity. TGM2 serves as a critical regulator of osteogenic differentiation potential and mitochondrial function in BMMSCs derived from T2DM rats BMMSCs were isolated and purified from femurs of the normal and T2DM rats, and then cultured in osteogenic induction medium for 7 days. BMMSCs from normal rats were used as the control group.