age-related skeletal dynamics and decrease in bone strength in dna repair deficient male trichothiodystrophy mice与年龄相关的骨骼动力学和骨强度下降在dna修复缺陷男性trichothiodystrophy老鼠.pdfVIP

Age-Related Skeletal Dynamics and Decrease in Bone Strength in DNA Repair Deficient Male Trichothiodystrophy Mice 1. 2. 2 3 4 Claudia Nicolaije , Karin E. M. Diderich , S. M. Botter , Matthias Priemel , Jan H. Waarsing , 4 2 3 4 1 Judd S. Day , Renata M. C. Brandt , Arndt F. Schilling , Harrie Weinans , Bram C. Van der Eerden , 2 2 1 Gijsbertus T. J. van der Horst , Jan H. J. Hoeijmakers , Johannes P. T. M. van Leeuwen * 1 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands, 2 MGC Department of Cell Biology Genetics, Center for Biomedical Genetics, Erasmus MC, Rotterdam, The Netherlands, 3 Department of Trauma, Hand, and Reconstructive Surgery, School of Medicine, Hamburg University, Hamburg, Germany, 4 Department of Orthopedics, Erasmus MC, Rotterdam, The Netherlands Abstract Accumulation of DNA damage caused by oxidative stress is thought to be one of the main contributors of human tissue aging. Trichothiodystrophy (TTD) mice have a mutation in the Ercc2 DNA repair gene, resulting in accumulation of DNA damage and several features of segmental accelerated aging. We used male TTD mice to study the impact of DNA repair on bone metabolism with age. Analysis of bone parameters, measured by micro-computed tomography, displayed an earlier decrease in trabecular and cortical bone as well as a loss of periosteal apposition and a reduction in bone strength in TTD mice with age compared to wild type mice. Ex vivo analysis of bone marrow differentiation pote