DATE: August 19, 2021
TIME: 8:00am PT, 11:00am ET
Type 2 diabetes mellitus (T2D) is associated with an increased risk of osteoporotic fractures. Several factors have been identified as being potentially responsible for this increased risk, including alterations in bone remodelling that may be induced by changes in circulating glucose and/or presence of non-enzymatic crosslinks known as advanced glycation end-products (AGEs). This study aims to assess whether these variations alter gene expression related to bone remodeling and glycation in osteocytes, the primary orchestrators of the bone turnover process. We hypothesized that hyperglycemia would upregulate key markers of bone remodelling and glycation. In three independent experiments, Ocy454-12H osteocytes were grown in complete α-MEM media with 22mM Mannitol (Osmotic Control) and 22mM glucose with 25mM HEPES to maintain pH. Cells were grown for 9 days before measurement of gene expression. Real-time PCR for remodeling markers (sclerostin [SOST], osteoprotegerin [OPG], and receptor activator of nuclear Kappa-β ligand [RANKL]) and glycation markers (receptor for advanced glycation end-products [RAGE] and AGE clearance receptor [AGER1]) was performed using SYBR green, and β-actin was used as a housekeeping gene. Our results indicate disruptions in bone turnover, favoring increased resorption and a potential deterioration in bone quality. Increased RAGE suggests that hyperglycemia activates RAGE-induced signaling mechanisms that cause cell stress and contribute to cell dysfunction, ultimately making cells more susceptible to the harmful effects of AGEs. However, the upregulation of AGER1, which accelerates removal of AGEs and inhibits RAGE signaling, may provide some defense against AGEs formed in hyperglycemia. Together, these results show for the first time in a mature osteocyte cell line that high glucose concentrations representative of T2D may profoundly affect osteocytes.
- Understanding how diabetes affect bone health
- Understanding advance glycation end products and their harmful effects on health
- Learning about osteocytes
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