1977-P: Methylglyoxal May Contribute to Bone Loss via Differential Effects on Osteoblast and Osteoclasts

Purpose of the Study: Diabetes mellitus is characterized by chronic hyperglycemia and diabetic complications. Methylglyoxal (MG) is a reactive advanced glycation end-product precursor in which abnormal accumulation is found in the serum of diabetic patients. In clinical studies, they are found to have higher risk of bone fracture. Yet, the underlying mechanism has not been elucidated. Bone remodeling, depending on the interaction between osteoblast (OB) and osteoclast (OC), is to maintain bone structural integrity, such to resorb aged cells while replacing with newly formed cells and to support the metabolic function of bones. Both OB and OC were found to be severely affected by MG. Hence the effect of MG leading to subsequent bone loss was investigated. Methods: In this study, the effects of MG on bone in both animal and cell models were investigated. SD rats were treated with MG (50mM, 10mL/kg) for 8 weeks. Proximal end of tibia were collected for analysis. The bone mineral density (BMD) and mRNA expression of bone biomarkers were measured using micro-CT and RT-PCR respectively. Results: Using micro-CT scanning, MG-treated group has lower trabecular BMD (318.1 ± 10.9 mg HA/ccm) compared with control group (383.2 ± 17.7 mg HA/ccm). Using RT-PCR, it was found there were decreased expressions in OB biomarkers including Bone Gamma-Carboxyglutamate Protein (0.718 fold), Collagen I (0.25 fold); while increasing RANKL/OPG (9.46 fold) and Sclerostin (3.51 fold) after MG treatment, indicating the inhibition of bone formation. Besides, increased expressions in OC biomarkers Cathepsin K (1.51 fold), Osteoclast-associated receptor (1.90 fold), Receptor activator of nuclear factor kappa B (1.34 fold) and Tartrate-resistant acid phosphatase (2.57 fold) were observed indicating activation of OC. Conclusions: MG activates OC and inhibits OB, leading to lower BMD and more porous bone architecture. Therefore, MG may contribute to the bone loss through imbalanced bone remodeling in both OC and OB. Disclosure K. Yue: None. F. Lee: None.