Impact of Hyperglycemia on Rat Cortical Bone Microstructure and Osteoprogenitor Cell Exhaustion
Uncontrolled diabetes has been associated with an increased risk of bone fracture and implant failure. However, the underlying reasons have yet to be entirely understood. Our group previously reported that osteocyte number appeared increased in the peri-implant bone of hyperglycemic rats, which might increase cellular level cortical porosity. In this context, since there are examples of increased proliferation of cells in hyperglycemia from other tissues, we hypothesized that increased osteocyte cell number due to the excessive proliferation of osteoprogenitors increases osteocyte lacunar density in hyperglycemic bone. To address the hypothesis, changes in bone porosity, due to osteocyte lacunar density and vascular canal volume, in streptozotocin (STZ)-induced hyperglycemic Wistar Albino rat bone were quantitatively assessed with synchrotron radiation (SR) micro-CT. Additionally, the effects of hyperglycemia on bone formation in osteogenic cultures of rat bone marrow stromal cells (rBMSCs) was quantified. To elucidate the mechanism by which hyperglycemia affects progenitor cells, colony forming capacity, glucose consumption, motility, and whole transcriptome of rBMSCs were compared with euglycemic controls. As opposed to the hypothesis, lacunar density was significantly higher in STZ than euglycemic group (67,195±3,206 vs. 61,126±1,457, lacuna number/mm3, p
Bone Biology, bone formation, cellular exhaustion, cortical porosity, Hyperglycemia, Synchrotron radiation micro-CT
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