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

• Published in: Journal of cellular biochemistry Vol. 117; no. 3; p. 721
• Main Authors: Hurley, Marja M, Gronowicz, Gloria, Zhu, Li, Kuhn, Liisa T, Rodner, Craig, Xiao, Liping
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01.03.2016
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25357

FGF-2 stimulates preosteoblast replication, and knockout of the FGF-2 gene in mice resulted in osteopenia with age, associated with decreased Wnt-[beta]-Catenin signaling. In addition, targeted expression of FGF-2 in osteoblast progenitors increased bone mass in mice via Wnt-[beta]-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 [beta]-catenin, which can enhance bone formation, we also assessed its age-related expression in HMDPCs. An age-related decrease in total-[beta]-Catenin mRNA and protein expression was observed. However there were increased levels of p-[beta]-Catenin and decreased levels of activated-[beta]-Catenin in old HMDSCs. FGF-2 treatment increased FGFR1 and [beta]-Catenin protein, reduced the level of p-[beta]-Catenin and increased activated-[beta]-Catenin in aged HMDPCs. In conclusion, reduction in FGF-2 expression could contribute to age-related impaired function of HMDPCs via modulation of Wnt-[beta]-catenin signaling. J. Cell. Biochem. 117: 721-729, 2016. © 2015 Wiley Periodicals, Inc.