Age-Related Changes in FGF-2, Fibroblast Growth Factor Receptors and ?-Catenin Expression in Human Mesenchyme-Derived Progenitor Cells.

ABSTRACT: FGF-2 stimulates preosteoblast replication, and knockout of the FGF-2 gene in mice resulted in osteopenia with age, associated with decreased Wnt-?-Catenin signaling. In addition, targeted expression of FGF-2 in osteoblast progenitors increased bone mass in mice via Wnt-?-Catenin signaling. We posited that diminution of the intrinsic proliferative capacity of human mesenchyme-derived progenitor cells (HMDPCs) with age is due in part to reduction in FGF-2. To test this hypothesis HMDPCs from young (27-38), middle aged (47-56), and old (65-76) female human subjects were isolated from bone discarded after orthopedic procedures. HMDPCs cultures were mostly homogeneous with greater than 90% mesenchymal progenitor cells, determined by fluorescence-activated cell sorting. There was a progressive decrease in FGF-2 and FGFR1 mRNA and protein in HMDPCs with age. Since FGF-2 activates ?-catenin, which can enhance bone formation, we also assessed its age-related expression in HMDPCs. An age-related decrease in total-?-Catenin mRNA and protein expression was observed. However there were increased levels of p-?-Catenin and decreased levels of activated-?-Catenin in old HMDSCs. FGF-2 treatment increased FGFR1 and ?-Catenin protein, reduced the level of p-?-Catenin and increased activated-?-Catenin in aged HMDPCs. In conclusion, reduction in FGF-2 expression could contribute to age-related impaired function of HMDPCs via modulation of Wnt-?-catenin signaling.

SUBMITTER: Hurley MM 

PROVIDER: S-EPMC4861164 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature