Age-related bone deterioration is diminished by disrupted collagen sensing in integrin alpha 2 beta 1 deficient

作者：Stange Richard^*; Kronenberg Daniel; Timmen Melanie; Everding Jens; Hidding Heriburg; Eckes Beate; Hansen Uwe; Holtkamp Michael; Karst Uwe; Pap Thomas; Raschke Michael J

来源：Bone, 2013, 56(1): 48-54.

DOI：10.1016/j.bone.2013.05.003

• Bone metabolism
• Aging
• Collagen-binding integrins
• Collagen type I
• Osteoporosis

Collagen binding integrins are of essential importance in the crosstalk between cells and the extracellular matrix. Integrin alpha 2 beta 1 is a major receptor for collagen I, the most abundant protein in bone. In this study we show for the first time that integrin alpha 2 deficiency is linked to collagen type I expression in bone. Investigating the femurs of wild type and integrin alpha 2 beta 1deficient mice, we found that loss of integrin a2 results in altered bone properties. Histomorphometric analysis of integrin a2 long bones displayed more trabecular network compared to wild type bones. During age related bone loss the integrin alpha 2 beta 1 deficient bones retain trabecular structure even at old age. These findings were supported by functional, biomechanical testing, wherein the bones of integrin alpha 2 beta 1 deficient mice do not undergo age-related alteration of biomechanical properties. These results might be explained by the increased presence of collagen in integrin alpha 2 beta 1 deficient bone. Collagen type I could be detected in higher quantities in the integrin alpha 2 beta 1 deficient bones, forming abnormal, amorphous fibrils. This was linked to higher expression levels of collagen type I and other bone formation related proteins as alkaline phosphatase of integrin alpha 2 beta 1 deficient osteoblasts. Osteoclasts of integrin alpha 2 beta 1 deficient mice did not show any differences. Consequently these results indicate that the absence of integrin alpha 2 beta 1 alleviates the effects of age related bone degradation through over-expression of collagen type I and demonstrate a molecular mechanism how collagen binding integrins might directly impact bone aging.

• 出版日期2013-9