4.4 Article

Effects of hyperglycemia on bone metabolism and bone matrix in goldfish scales

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.cbpa.2016.09.010

Keywords

Alloxan; Bone metabolism; Bone model; Diabetes; Fish scales; Glycation of matrix collagen; Hyperglycemia; Increased fracture rate; Type 1 collagen

Funding

  1. Japan Society for the Promotion of Science [24500848, 15K01705]
  2. Grants-in-Aid for Scientific Research [24500848, 15K01705] Funding Source: KAKEN

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Increased risk of fracture associated with type 2 diabetes has been a topic of recent concern. Fracture rislc is related to a decrease in bone strength, which can be affected by bone metabolism and the quality of the bone. To investigate the cause of the increased fracture rate in patients with diabetes through analyses of bone metabolism and bone matrix protein properties, we used goldfish scales as a bone model for hyperglycemia. Using the scales of seven alloxan-treated and seven vehicle-treated control goldfish, we assessed bone metabolism by analyzing the activity of marker enzymes and mRNA expression of marker genes, and we measured the change in molecular weight of scale matrix proteins with SDS-PAGE. After only a 2-week exposure to hyperglycemia, the molecular weight of alpha- and beta-fractions of bone matrix collagen proteins changed incrementally in the regenerating scales of hyperglycemic goldfish compared with those of euglycemic goldfish. In addition, the relative ratio of the gamma-fraction significantly increased, and a delta-fraction appeared after adding glyceraldehyde a candidate for the formation of advanced glycation end products in diabetes to isolated type 1 collagen in vitro. The enzymatic activity and mRNA expression of osteoblast and osteoclast markers were not significantly different between hyperglycemic and euglycemic goldfish scales. These results indicate that hyperglycemia is likely to affect bone quality through glycation of matrix collagen from an early stage of hyperglycemia. Therefore, non-enzymatic glycation of collagen fibers in bone matrix may lead to the deterioration of bone quality from the onset of diabetes. (C) 2016 Elsevier Inc. All rights reserved.

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