Influence of high glucose on 1,25-dihydroxyvitamin D3-induced effect on human osteoblast-like MG-63 cells

Abstract

Impaired bone formation due to defective osteoblast function, as reflected in a decreased serum osteocalcin (OC) concentration in the patients with diabetes, has been implicated in the development of diabetic osteopenia. The role of hyperglycemia in this decrease in serum OC concentration was investigated. 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), an active form of vitamin D3, stimulated OC secretion from the human osteosarcoma cell line MG-63 in a dose-dependent manner. Exposure of the cells to high concentrations of glucose for 7 days significantly impaired 1,25(OH)2D3-induced OC secretion as compared with that observed with cells maintained under normal glucose (5.5 mM) or high mannitol conditions. The inhibitory effect of glucose was in a dose-dependent manner up to 55 mM. High glucose (55 mM) also attenuated the 1,25(OH)2D3-induced increase in OC mRNA abundance in MG-63 cells, suggesting that the inhibition of the 1,25(OH)2D3-induced increase in OC secretion by exposure to a high concentration of glucose was, at least in part, mediated at the transcriptional level. High glucose significantly decreased the number of 1,25(OH)2D3 receptors in MG-63 cells, without any change in the dissociation constant for 1,25(OH)2D3; this effect was not mimicked by high mannitol, indicating specificity for glucose. These observations suggest that a high glucose concentration significantly impairs the ability of osteoblastic cells to synthesize OC in response to 1,25(OH)2D3 by reducing 1,25(OH)2D3 receptor number, and that impaired cell function caused by sustained exposure to high glucose contributes to the defect in bone formation observed in the patients with diabetic osteopenia.

Impact of Non-Insulin Dependent Diabetes Mellitus on Bone Structure Biomarkers in Postmenopausal Obese Women

“…These results are consistent with several previous studies that reported low osteocalcin [38][39][40][41][42][43][44] and P1NP [45,46] among patients with NIDDM. Our finding that supports the concept of lower bone formation biomarkers in NIDDM than non-diabetics was due to impaired osteoblast function associated with high glucose levels among diabetics [47][48][49]. Moreover, we found that CTX and NTX as bone turn over markers for bone resorption were significantly lower in diabetic patients than non-diabetic patients, so that these results indicate delayed bone destruction in patients with NIDDM.…”

Women with type 2 diabetes mellitus have lower cortical porosity of the proximal femoral shaft using low-resolution CT than nondiabetic women, and increasing glucose is associated with reduced cortical porosity

“…It is also well established that AGEs increase with age and that glycation is associated with altered osteoblast activity [9], and high glucose in vitro might increase apoptosis of osteoblasts [15,48].…”

Bone metabolism and fracture risk in type 2 diabetes mellitus [Review]

“…We also clinically found that serum adiponectin was associated with BMD, bone turnover, and the presence of vertebral fractures (VFs) in T2DM patients [25]. Moreover, high glucose was experimentally shown to impair OC expression and secretion from osteoblastic cells [26], and treatments for hyperglycemia in T2DM patients were found to enhance their serum OC level [27]. We found that serum adiponectin level before starting to compensate poorly controlled T2DM could predict the subsequent increase in serum OC level during glycemic control [28].…”