Osteogenic response of bone marrow stromal cells from normal and ovariectomized rats treated with a low dose of basic fibroblast growth factor.
Basic fibroblast growth factor (bFGF) is a potent mitogen that exhibits stimulatory effects on bone tissue regeneration. To gain further insight into the potential of bFGF for systemic therapy in osteoporosis, we investigated the responsiveness of bone marrow stromal cells (BMSCs) explanted from 7-month-old normal and ovariectomized (OVX) rats that were intravenously treated with a low dose of bFGF (25 microg/kg) for 2 weeks. The BMSCs were obtained using femoral aspiration and maintained in an osteogenic medium. The amount of cells recovered from bFGF-treated rats was lower than that from saline-treated rats, and proliferation of the cells was markedly less for the bFGF-treated rats. The BMSCs from the bFGF-treated rats also showed lower levels of specific alkaline phosphatase (ALP) activity (ALP/deoxyribonucleic acid) and mineralization. Expression of the extracellular matrix proteins critical for mineralization, in particular osteopontin, was greater for bFGF-treated cells from both types of animals in the first week of culture, after which the expression of all markers significantly declined. Dual energy x-ray absorptiometry analyses of the tibiae showed an increase in bone mineral density after bFGF treatment only for OVX rats. We conclude that osteoprogenitor cells were depleted from the marrow of bFGF-treated rats, most likely because of the stimulatory effect of bFGF on bone formation.
Varkey
Mathew
M
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada.
Kucharski
Cezary
C
Doschak
Michael R
MR
Winn
Shelley R
SR
Brochmann
Elsa J
EJ
Murray
Samuel
S
Matyas
John R
JR
Zernicke
Ronald F
RF
Uludag
Hasan
H
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods
D016222:Fibroblast Growth Factor 2