Make Therapy Strategies on Osteogenesis, Osteoclastogenesis, and Angiogenesis of Diabetes Basing on the Specificity of Mesenchymal Stem Cells from Diabetic Patients

Diabetic patients often experience osteopenia, which is associated with increased risk of bone fractures and delayed fracture repair. Type 1 diabetes has frequently been shown to be associated with decreased bone mineral density (BMD). On the other hand, whether this occurs in type 2 diabetes is controversial. mRNA expression of alkaline phosphatase (ALP) and osteocalcin (OCN) was significantly lower in the DM rat group than in the control group. Human endothelial progenitor cells (EPC) from Type 2 diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Abnormalities of bone and blood vessel as a result of diabetes are well-known, but the mechanisms responsible for them are unclear. Clinically, hyperbaric oxygen (HBO) has a positive effect on wound healing in diabetic foot with infection and decreases blood glucose in patients with DM and hypertension. In the present study we will further investigate the effect of HBO, GSK-3P activator (sodium nitroprusside dehydrate, SNP), GSK-3P inhibitors (CHIR99021 and SB-216763) on osteogenesis, osteoclastogenesis, and angiogenesis of diabetes basing on the specificity of stem cells from diabetic patients. Our preliminary microarray data from diabetic mesenchymal stem cells (MSCs) showed that HBO treatment modulates the expression of canonical Wnt (Wnt 3a) and non-canonical Wnt (Wnt 5a) signaling related genes, OSF gene, and VEGF gene. Our western blotting data showed that the protein level of Runx2 was up-regulated and GSK-3P was down-regulated after HBO treatment. These data suggested that HBO treatment increases the osteogenesis of diabetic MSCs by Wnt signaling regulation. We will establish a 3-year’s study for analysis of HBO effects on osteogenesis, angiogenesis, and osteoclastogenesis of stem cells in different pathway: 1. For the first year: related to osteogenesis To investigate the HBO effect on osteogenesis of diabetic MSCs 2. For the second year: related to angiogenesis To investigate the HBO effect on angiogenesis of diabetic EPCs 3. For the first year: related to osteoclastogenesis To investigate the HBO effect on osteoclastogenesis of diabetic mononuclear cells 

Project ID:PC10007-0392 
External Project ID:NSC100-2314-B182-006-MY3