Effects of matrix advanced glycation end products on human osteoclast resorption of human cortical bone
Long lived proteins, such as collagen, are especially susceptible to Advanced Glycation End-Products (AGEs) formation. Cross-links in collagen induced by AGEs may lead to changes in mechanical properties of bone, such as reduced toughness, reduced ductility and increased fragility. In addition, delayed bone healing by aging and diabetes may also be due to AGEs build up, suggesting a detrimental effect of AGEs on bone remodeling process, by acting on bone cells (e.g. osteoclasts and osteoblasts). Such detrimental effects on osteoblasts have been well documented; however AGEs effect on osteoclasts remains unclear. The hypothesis of this study is that AGEs accumulate with increasing age in bone matrix and such matrix AGEs enhance osteoclast resorption activity in bone. To test the hypothesis, pre-osteoclasts were seeded directly on human cadaveric bone slices (6mm diameter × 0.15mm thickness) from three age groups with all necessary differentiating factors (RANKL & MCSF) for 14 days. The amount of resorption area, number and size of resorption pits were measured on each bone slice by light microscope. Next, the samples were demineralized and AGEs autofluorescence was measured at each resorption pit. In addition, the amount of AGEs released from osteoclastic bone resorption was estimated. The results showed that osteoclastic bone resorption was independent of the matrix AGEs concentration, however tissue age may have an effect on osteoclastic activities.