Effects of C-peptide replacement therapy on bone microarchitecture parameters in streptozotocin-diabetic rats.

Abstract

Pathological pathways involved in the development of diabetic complications are still unclear. Several studies suggested a pathogenic role of C-peptide deficiency in vascular and neuropathic complications. However, to date, the role of C-peptide on diabetes-related bone loss has not been investigated. The objective of this study was to test the effects of a 6-week regimen of rat C-peptide infusion on bone by combining micro-CT imaging with histological testing. Twenty-three, four-month-old male Wistar rats were randomly divided into three groups: Normal control group; Sham diabetic control group; Diabetic plus C-peptide group. Diabetes was induced by injection of streptozotocin. Rat C-peptide was delivered via subcutaneously osmopumps. We assessed several trabecular microarchitectural parameters and cellular and matrix proteins in bone tissue sections. At the end of the study, both the normal control and diabetic plus C-peptide groups had a higher tibia weight than the diabetic control group (p = 0.05 and p = 0.02, respectively). C-peptide levels significantly and positively correlated with the trabecular thickness (r= 0.45, p=0.08) and negatively with structure model index (r= -0.40, p=0.09). Furthermore, it positively correlated with one of the histological assessments (i.e. PLIN1 score; p=0.02). Micro-CT evaluation showed significant inter-group differences in trabecular thickness (p=0.02), trabecular space (p = 0.05) and cross-sectional thickness (p=0.05). Diabetic plus C-peptide group showed a higher trabecular thickness (p<0.001), cross-sectional thickness (p=0.03) and a lower trabecular space (p=0.05) than the normal control group. Both the normal control and diabetic plus C-peptide groups had more Runx-2 and PLIN1 positive cells in comparison to the diabetic control group (p = 0.045 and p = 0.034). For the first time we demonstrated that the diabetic rats receiving rat C-peptide had higher quality of trabecular bone, than diabetic rats not receiving it. C-peptide could have a role in the prevention of diabetes-related bone loss.