Advanced glycation end products in musculoskeletal system and disorders

The human population is ageing globally, and the number of old people is increasing yearly. Diabetes is common in the elderly, and the number of diabetic patients is also increasing. Elderly and diabetic patients often have musculoskeletal disorder, which are associated with advanced glycation end products (AGEs). AGEs are heterogeneous molecules derived from non-enzymatic products of the reaction of glucose or other sugar derivatives with proteins or lipids, and many different types of AGEs have been identified. AGEs are a biomarker for ageing and for evaluating disease conditions. Fluorescence, spectroscopy, mass spectrometry, chromatography, and immunological methods are commonly used to measure AGEs, but there is no standardized evaluation method because of the heterogeneity of AGEs. The formation of AGEs is irreversible, and they accumulate in tissue, eventually causing damage. AGE accumulation has been confirmed in neuromusculoskeletal tissues, including bones, cartilage, muscles, tendons, ligaments, and nerves, where they adversely affect biomechanical properties by causing charge changes and forming cross-linkages. AGEs also bind to receptors, such as the receptor for AGEs (RAGE), and induce inflammation by intracellular signal transduction. These mechanisms cause many varied aging and diabetes-related pathological conditions, such as osteoporosis, osteoarthritis, sarcopenia, tendinopathy, and neuropathy. Understanding of AGEs related pathomechanism may lead to develop novel methods for the prevention and therapy of such disorders which affect patients' quality of life. Herein, we critically review the current methodology used for detecting AGEs, and present potential mechanisms by which AGEs cause or exacerbate musculoskeletal disorders.