Is there an autoimmune process in bone? Gene expression studies in diabetic and nondiabetic BB rats as well as BB rat-related and -unrelated rat strains

Abstract

It is well known that type 1 diabetes is associated with a decrease in bone mass and delayed healing of fractures in human and in animal models of type 1 diabetes. Using well- and poorly compensated diabetic BB/O(ttawa) K(arlsburg) rats spontaneously developing insulin-dependent type 1 diabetes, it was recently shown that, in contrast to all other tissues studied, bone is most influenced by metabolic state and seems to be regulated in a manner different from other organs. Therefore, we studied the expression of additional genes (Bmp-1, Bmp-4, Vegf, Bglap, Il-1b, Infg, Tnfa, Calca, Sp1, Yy1) in bone of nondiabetic BB rats compared with newly diagnosed and well- and poorly compensated diabetic rats as well as two nondiabetes-prone congenic BB.SHR rats, BB rat-related (WOKW) and -unrelated rat strains (F344). Six males of each group were euthanized, the tibial bone was removed, and total RNA was extracted, transcribed in complementary DNA, and used for real-time PCR. In a comparison of nondiabetic with diabetic groups, the relative gene expression was reduced by >80% in newly diagnosed and in well-compensated diabetic BB/OK rats. The gene expression in poorly compensated rats increased significantly in 7 of 10 genes and was comparable with those of nondiabetic BB/OK rats. In a comparison of gene expression between diabetes-prone BB/OK and nondiabetes-prone BB.1K, BB.4S, WOKW, and F344 rats, there were no significant differences between newly diagnosed and well-compensated BB/OK diabetic rats and nondiabetic BB.1K, BB.4S, WOKW, and F344 rats. On the basis of these findings, we concluded that spontaneous diabetes influences bone gene expression in BB/OK rats, which may be attributed to the genetically determined autoimmune process not only affecting pancreatic beta-cells but also bone formation and resorption.