Age-Related Changes in FGF-2, Fibroblast Growth Factor Receptors and β-Catenin Expression in Human Mesenchyme-Derived Progenitor Cells.
FGF-2 stimulates preosteoblast replication, and knockout of the FGF-2 gene in mice resulted in osteopenia with age, associated with decreased Wnt-β-Catenin signaling. In addition, targeted expression of FGF-2 in osteoblast progenitors increased bone mass in mice via Wnt-β-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 β-catenin, which can enhance bone formation, we also assessed its age-related expression in HMDPCs. An age-related decrease in total-β-Catenin mRNA and protein expression was observed. However there were increased levels of p-β-Catenin and decreased levels of activated-β-Catenin in old HMDSCs. FGF-2 treatment increased FGFR1 and β-Catenin protein, reduced the level of p-β-Catenin and increased activated-β-Catenin in aged HMDPCs. In conclusion, reduction in FGF-2 expression could contribute to age-related impaired function of HMDPCs via modulation of Wnt-β-catenin signaling.
Department of Medicine, UCONN Health, Farmington, CT.
Marja M
MM
Hurley
Department of Surgery, UCONN Health, Farmington, CT.
Gloria
G
Gronowicz
Department of Reconstructive Sciences, UCONN Health, Farmington, CT.
Li
L
Zhu
Department of Reconstructive Sciences, UCONN Health, Farmington, CT.
Liisa T
LT
Kuhn
Department of Orthopedics, UCONN Health, Farmington, CT.
Craig
C
Rodner
Department of Medicine, UCONN Health, Farmington, CT.
Liping
L
Xiao
D000328:Adult; D000368:Aged; D000375:Aging; D002478:Cells, Cultured; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C495270:CTNNB1 protein, human; D051176:beta Catenin; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
AGING; ENDOGENOUS FIBROBLAST GROWTH FACTOR-2; FIBROBLAST GROWTH FACTOR RECEPTOR; HUMAN MESENCHYME-DERIVED PROGENITOR CELLS; β-CATENIN