Health Science Campus
Room # 1711
1125 Hospital Drive
Toledo, OH 43614
Diabetes, obesity, and osteoporosis are major public health concerns due to their prevalence in our increasingly sedentary and aging society. The peroxisome proliferator-activated receptor-gamma (PPARγ) transcription factor is a key regulator of glucose metabolism and energy expenditure. This protein also regulates lineage commitment of bone marrow mesenchymal stem cells (MSC). We have demonstrated that PPARγ protein is involved in changing of MSC phenotype observed during aging and diabetic disease. Changes in the MSC phenotype include shifting of the MSC differentiation potential toward adipocyte (fat cells) and away from osteoblasts (bone forming cells) which leads to the bone loss with simultaneous accumulation of fat in bone cavities. PPARγ protein is a target for a class of anti-diabetic drugs TZDs which decrease glucose levels and increase insulin sensitivity. Although their beneficial anti-diabetic profile is evident, prolonged treatment with these drugs leads to the bone loss and increased number of bone fractures in diabetic patients. We have demonstrated that similarly to aging, TZDs affect bone mass by changing differentiation pattern of bone marrow MSC. The research in our laboratory is dedicated to:
- Understanding and manipulating molecular mechanisms which are responsible for age- and diabetes-related changes in MSC potential for new bone formation.
- Development of new methods to improve bone fracture healing in diabetic patients by means of stem cell-based and siRNA-based therapies.
- Testing different methods for therapeutic interventions to prevent bone loss associated with an anti-diabetic TZD therapy.