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.

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Year

Entry

1994

Parfitt AM. The two faces of growth: benefits and risks to bone integrity. Osteoporos Int. November 1994;4(6):382-398.

1997

Norman TL, Wang Z. Microdamage of human cortical bone: incidence and morphology in long bones. Bone. April 1997;20(4):375-379.

1994

Parfitt AM. Osteonal and hemi‐osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem. July 1994;55(3):273-286.

1989

Sell DR, Monnier VM. Structure elucidation of a senescence cross-link from human extracellular matrix: implication of pentoses in the aging process. J Biol Chem. December 25, 1989;264(36):21597-21602.

2006

Seeman E, Delmas PD. Bone quality: the material and structural basis of bone strength and fragility. NEJM. May 25, 2006;354(21):2250-2261.