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

Abstract

BackgroundType 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fracture. Several factors have been identified as being potentially responsible for this risk, such as alterations in bone remodelling that may have been induced by changes in circulating glucose or/and by the presence of non-oxidative end products of glycosylation (AGEs). The aim of this study is to assess whether such variations generate a change in the gene expression related to the differentiation and osteoblast activity (OPG, RANKL, RUNX2, OSTERIX, and AGE receptor) in primary cultures of human osteoblast-like cells (hOB).MethodsWe recruited 32 patients; 10 patients had osteoporotic hip fractures (OP group), 12 patients had osteoporotic hip fractures with T2DM (T2DM group), and 10 patients had hip osteoarthritis (OA group) with no osteoporotic fractures and no T2DM. The gene expression was analyzed in hOB cultures treated with physiological glucose concentration (4.5 mM) as control, high glucose (25 mM), and high glucose plus AGEs (2 μg/ml) for 24 h.ResultsThe hOB cultures from patients with hip fractures presented slower proliferation. Additionally, the hOB cultures from the T2DM group were the most negatively affected with respect to RUNX2 and OSX gene expression when treated solely with high glucose or with high glucose plus AGEs. Moreover, high levels of glucose induced a major decrease in the RANKL/OPG ratio when comparing the OP and the T2DM groups to the OA group.ConclusionsOur data indicates an altered bone remodelling rate in the T2DM group, which may, at least partially, explain the reduced bone strength and increased incidence of non-traumatic fractures in diabetic patients.

Hyperglycemia-related advanced glycation end-products is associated with the altered phosphatidylcholine metabolism in osteoarthritis patients with diabetes

“…In cell and animal studies, AGEs have been implicated as key pathogenic factors in initiation and progression of OA and DM [ 28 , 37 ]. The main mechanisms involve altered function of many intra- and extracellular proteins and generation of reactive oxygen species (ROS) by the activation of the receptor for AGEs (RAGE) [ 13 ].…”

Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties

“…As mentioned above, high glucose concentrations lead to the creation of AGEs in bone matrix. Human osteoblasts treated with high glucose concentration and/or AGEs show a reduced expression of pro-osteogenic markers such as Runx2 and Osterix (65, 66). More critically, AGEs increase the rate of apoptosis of osteoblasts and its precursor cells (67, 68).…”

Diabetes Mellitus-induced Bone Fragility

“…Furthermore, primary cultured human osteoblast-like cells (hOBs) from patients with T2DM and hip fractures showed slower proliferation and a lower expression of Runx2 and osterix when treated with high glucose or high glucose plus AGEs. Furthermore, high glucose induced a marked decrease in the receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) ratio in hOBs from patients with T2DM and hip fractures compared with those with hip fractures without DM ( 56 ). In addition, peripheral blood-derived mesenchymal stem cells isolated from patients with T2DM showed a significant decrease in the potential for differentiation toward osteoblasts, with lower levels of alkaline phosphatase (ALP), type 1 collagen, and osteocalcin as well as decreased mineralization compared with subjects without DM ( 57 ).…”