BMP2Gene Therapy on the Repair of Bone Defects of Aged Rats |
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Authors: | B Yue B Lu K R Dai X L Zhang C F Yu J R Lou T T Tang |
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Institution: | (1) Department of Orthopedics, Ninth People’s Hospital, Shanghai Second Medical University, Shanghai, People’s Republic of China;(2) Health Science Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Second Medical University, Shanghai, People’s Republic of China;(3) Department of Orthopedic Surgery, Washington University School of Medicine, St. Louis, MO, USA |
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Abstract: | Age-related decline in the number of mesenchymal stem cells (MSCs) and their reduced capability to differentiate osteogenically,
along with diminished availability of growth factors, may be major factors accounting for reduced bone formation in the aging
mammalian body. In the first part of the study, we compared the number of MSCs in bone marrow (BM) and the content of bone
morphogenetic protein 2 (BMP2) in cortical bone tissue in juvenile, adult, and aged (1, 9, and 24 months, respectively) male
rats. To assay the influence of aging on osteogenic differentiation ability, MSCs from the three age groups were transduced
with the BMP2 gene. Following gene transduction, the production of BMP2 in culture media, expression of osteogenic proteins (e.g., alkaline
phosphatase, type Iα1 collagen, osteopontin, and bone sialoprotein), as well as ectopic bone formation in athymic mice were
compared. Results showed that the number of MSCs in BM as well as the content of BMP2 in cortical bone tissue decreased with
age, but no significant differences between the three age groups were found with regard to production of BMP2 or capability
of BMP2 gene-modified MSCs to differentiate osteogenically. The second part of the study applied BMP2 gene-modified autologous MSCs/β-tricalcium phosphate for repair of bone defects in aged rats with positive results. Our data
indicate that the osteogenic potential of MSCs of aged rats can be restored following BMP2 gene transduction and that this technique may be a useful approach in the future planning of gene therapy for age-related
osteoporotic fractures. |
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Keywords: | Aging BMP2 Mesenchymal stem cell Gene therapy Osteoporosis |
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