title: Age-related changes in the osteogenic differentiation potential of mouse bone marrow stromal cells.
abstract: Age-dependent bone loss has been well documented in both human and animal models. Although the underlying causal mechanisms are probably multifactorial, it has been hypothesized that alterations in progenitor cell number or function are important. Little is known regarding the properties of bone marrow stromal cells (BMSCs) or bone progenitor cells during the aging process, so the question of whether aging alters BMSC/progenitor osteogenic differentiation remains unanswered. In this study, we examined age-dependent changes in bone marrow progenitor cell number and differentiation potential between mature (3 and 6 mo old), middle-aged (12 and 18 mo old), and aged (24 mo old) C57BL/6 mice. BMSCs or progenitors were isolated from five age groups of C57BL/6 mice using negative immunodepletion and positive immunoselection approaches. The osteogenic differentiation potential of multipotent BMSCs was determined using standard osteogenic differentiation procedures. Our results show that both BMSC/progenitor number and differentiation potential increase between the ages of 3 and 18 mo and decrease rapidly thereafter with advancing age. These results are consistent with the changes of the mRNA levels of osteoblast lineage-associated genes. Our data suggest that the decline in BMSC number and osteogenic differentiation capacity are important factors contributing to age-related bone loss.
authors.affiliation: Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA.
authors.forename: Weixi
authors.initials: W
authors.lastname: Zhang
authors.forename: Guomin
authors.initials: G
authors.lastname: Ou
authors.forename: Mark
authors.initials: M
authors.lastname: Hamrick
authors.forename: William
authors.initials: W
authors.lastname: Hill
authors.forename: James
authors.initials: J
authors.lastname: Borke
authors.forename: Karl
authors.initials: K
authors.lastname: Wenger
authors.forename: Norman
authors.initials: N
authors.lastname: Chutkan
authors.forename: Jack
authors.initials: J
authors.lastname: Yu
authors.forename: Qing-Sheng
authors.initials: QS
authors.lastname: Mi
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Isales
authors.forename: Xing-Ming
authors.initials: XM
authors.lastname: Shi
mesh_terms: D000375:Aging; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D019070:Cell Lineage; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis; D012333:RNA, Messenger / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D012333:RNA, Messenger