AGE-RELATED-CHANGES IN OSTEOGENIC STEM-CELLS IN MICE

Osteoblasts arise from partially differentiated osteogenic progenitor cells (OPCs) which in turn arise from undifferentiated marrow stromal mesenchymal stem cells (MSCs), It has been postulated that age-related defects in osteoblast number and function may be due to quantitative and qualitative stem cell defects, To examine this possibility, we com pared osteogenic stern cell number and in vitro function in marrow cel ls from 4-month-old and 24-month-old male BALB/c mice, Histologic stud ies demonstrated that these mice undergo age-related bone loss resembl ing that seen in humans, In primary MSC cultures grown in media supple mented with 10 nM dexamethasone, cultures from older animals yielded a n average of 41% fewer OPC colonies per given number of marrow cells p lated (p < 0.001), This implies that for a given number of marrow cell s there are fewer stem cells with osteogenic potential in older animal s than there are in younger animals, The basal proliferative rate in c ultures from older animals, as measured by H-3-thymidine uptake, was m ore than three times that observed in cultures from young animals (p < 0.005), However, the increase in proliferative response to serum stim ulation was 10-fold in the younger cultures (p < 0.001) and insignific ant (p < 0.4) in the older cultures, Colonies in both age groups becam e alkaline phosphatase positive at the same rate, and virtually all co lonies were positive after 12 days of culture, Cultures from both age groups produced abundant type I collagen, These studies suggest that d efects in the number and proliferative potential of MSCs may underlie age-related defects in osteoblast number and function.