Imbalance of RANK, RANKL and OPG expression during tibial fracture repair in diabetic rats

Abstract

To clarify the mechanisms of altered bone repair in the diabetic state, we investigated RANK, RANKL and OPG expression by immunohistochemistry and RT-PCR in the fracture sites of rats that were either healthy or made diabetic by alloxan. Histomorphometric analysis of the fracture site at 7 days after fracture revealed that diabetic rats (db) have significantly less hard tissue formation at the fracture site, compared to controls. The number of RANK, RANKL and OPG positive cells was decreased in the db group; however, the RANKL/OPG ratio was similar in controls and db at this time. At day 14, numbers of RANKL and OPG positive cells and the mRNA expression for these markers were higher in the control group than in db (P = 0.008). The RANKL/OPG ratio in the db group was greater than in controls. Our results demonstrate an imbalance of RANKL/OPG expression associated with diabetes that may contribute to the delay of fracture repair during the course of diabetes.

Influence of high glucose and advanced glycation end-products (ages) levels in human osteoblast-like cells gene expression

“…These results indicate that high glucose suppresses bone resorption by decreasing RANKL expression, a decrease that seemed to be alleviated by the overstimulation of AGER when AGEs were added, as noticed by other authors [25]. In this regard, previous studies performed in osteoblastic and osteocyte cell lines [26] and in diabetic animals have demonstrated inconsistent results, showing both an increase and a decrease in the expression of OPG and RANKL [7, 9, 27] or no variation whatsoever [6]. The treatment with a high glucose medium plus AGEs produced a significant increase in OPG expression in the hOB cultures from the OP and T2DM groups.…”

“…Previous studies have pointed out that there is an imbalance in the RANKL/OPG ratio in the diabetic disease [6, 7, 9, 27]. To the best of our knowledge, no previous studies have been performed in hOB cultures from diabetic patients, although high OPG and low RANKL serum levels have been reported in patients with type 1 and type 2 diabetes [28, 29].…”

Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

“…Data on bone density in T1DM are controversial. Although the present findings are in agreement with a few previous studies (Gunczler et al, 1998;Gogas Yavuz et al, 2011;Loureiro et al, 2014;Souza et al, 2016), others found no significant decrease in BMD in individuals with T1DM when compared to controls (Bechtold et al, 2006;Brandao et al, 2007;Amorim et al, 2008;Maggio et al, 2010;Simmons et al, 2011). Some of these studies had limitations, such as sample sizes not sufficient to draw definitive conclusions regarding BMD.…”

Impact of type 2 diabetes on the gene expression of bone-related factors at sites receiving dental implants

“…Additionally, no clinical study has used the alveolar bone tissue from T2DM patients to investigate the expression of bone-related markers isolated from other events, such as the repair of critical-sized bone defects and other healing models. Additionally, bone biopsies are rarely undertaken in humans and most investigations analysing diabetic bone tissue have been performed in animal studies, 22,24,37,38 or have evaluated circulating bone-related markers in humans. 18,19,39 This investigation elucidated possible molecular mechanisms through which T2DM may interfere with bone tissue repair around implants under hyperglycaemic conditions.…”