decreased bone formation and osteopenia in lamin ac-deficient mice减少骨形成和骨量减少核纤层蛋白ac-deficient老鼠.pdfVIP

Decreased Bone Formation and Osteopenia in Lamin A/C-Deficient Mice 1. 2. 1 1 1 Wei Li , Li Sze Yeo , Christopher Vidal , Thomas McCorquodale , Markus Herrmann , Diane 2,3,4 1 Fatkin , Gustavo Duque * 1 Ageing Bone Research Program, Nepean Clinical School, University of Sydney, Penrith, New South Wales, Australia, 2 Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia, 3 Cardiology Department, St Vincent’s Hospital, Darlinghurst, New South Wales, Australia, 4 Faculty of Medicine, University of New South Wales, Kensington, New South Wales, Australia Abstract Age-related bone loss is associated with changes in bone cellularity with characteristically low levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although recent in vitro evidence has suggested a new role for proteins of the nuclear envelope in osteoblastogenesis, the role of these proteins in bone cells differentiation and bone metabolism in vivo remains unknown. In this study, we used the lamin A/C null (Lmna2/ 2) mice to identify the role of lamin A/C in bone turnover and bone structure in vivo. At three weeks of age, histological and micro computed tomography measurements of femurs in Lmna2/ 2 mice revealed a significant decrease in bone mass and microarchitecture in Lmna2/ 2 mice as compared with their wild type littermates. Furthermore, quantification of cell numbers after normalization with bone surface revealed a significant reduction in osteoblast and osteocyte numbers in Lmna2/ 2 mice compared with their WT littermates. In addition, Lmna2/ 2 mice have significantly lower osteoclast number, which show aberrant changes in their sha