Int J Med Sci 2019; 16(5):696-703. doi:10.7150/ijms.32707
Hyperglycemia inhibits osteoblastogenesis of rat bone marrow stromal cells via activation of the Notch2 signaling pathway
1. School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Taoyuan City 33302, Taiwan
2. Department of Orthopaedic Surgery, Chiayi Chang Gung Memorial Hospital, Chiayi County 61363, Taiwan
3. Department of Medical Research and Development, Chiayi Chang Gung Memorial Hospital, Chiayi County 61363, Taiwan
Huang KC, Chuang PY, Yang TY, Huang TW, Chang SF. Hyperglycemia inhibits osteoblastogenesis of rat bone marrow stromal cells via activation of the Notch2 signaling pathway. Int J Med Sci 2019; 16(5):696-703. doi:10.7150/ijms.32707. Available from https://www.medsci.org/v16p0696.htm
Background: Bone fragility and related fractures are increasingly being recognized as an important diabetic complication. Mesenchymal progenitors often serve as an important source of bone formation and regeneration. In the present study, we have evaluated the effects of diabetes on osteoblastogenesis of mesenchymal progenitors.
Methods: Primary bone marrow stromal cells (BMSCs) were isolated from control and streptozotocin-induced diabetic rats. These cells were evaluated for the effects of in vivo hyperglycemia on the survival and function of mesenchymal progenitors. We concomitantly investigated the effects of different concentrations of glucose, osmolality, and advanced glycation end product (AGE) on osteogenic differentiation and matrix mineralization of rat bone marrow mesenchymal stem cells (RMSC-bm). The relationship between the expression levels of Notch proteins and the corresponding ALP levels was also examined.
Results: Our results revealed that in vivo hyperglycemia increased cell proliferation rate but decreased osteogenic differentiation and matrix mineralization of primary rat BMSCs. In vitro high glucose treatment, instead of high AGE treatment, induced a dose-dependent inhibition of osteoblastogenesis of RMSC-bm cells. Activation of the Notch2 signaling pathway, instead of the Notch1 or osmotic response pathways, was associated with these diabetic effects on osteoblastogenesis of mesenchymal progenitors.
Conclusions: Hyperglycemia might inhibit osteoblastogenesis of mesenchymal progenitors via activation of the Notch2 signaling pathway.
Keywords: Diabetes mellitus, Hyperglycemia, Osteoblastogenesis, Mesenchymal Progenitor, Notch signaling pathway