The effect of bone morphogenetic protein-2, bone morphogenetic protein-7, parathyroid hormone, and platelet-derived growth factor on the proliferation and osteogenic differentiation of mesenchymal stem cells derived from osteoporotic bone.
BACKGROUND
It has been previously shown that in patients with osteoporosis, mesenchymal stem cell (MSC) growth rate and osteogenic potential is decreased contributing to inferior fracture consolidation. The aim of this study was to investigate the effect of bone morphogenetic protein-2 (BMP-2), BMP-7, parathyroid hormone (PTH), and platelet-derived growth factor (PDGF) on proliferation and osteogenic differentiation of MSCs derived from patients with osteoporosis.


METHODS
Trabecular bone was obtained from 10 patients (four males, mean age 76 years) with lower extremity osteoporotic fractures. MSCs were isolated by enzymatic digestion. Functional assays of proliferation and osteogenic differentiation were performed under the influence of a wide range of concentrations of BMP-2, BMP-7, PTH, and PDGF-BB. Proliferation was assessed using CFU-F and XTT assays. Osteogenic differentiation was assessed by alkaline phosphatase activity and total calcium production.


RESULTS
MSC proliferation was found to be stimulated by supplementation with BMP-7 and PDGF-BB, whereas BMP-2 and PTH had little effect. The largest increase in proliferation rate was observed after administration 100 ng/mL of BMP-7. All four molecules induced alkaline phosphatase activity and calcium production in growing osteoblasts with a dose-dependent effect noted. BMP-2 and BMP-7 at their highest studied concentration (100 ng/mL) produced a threefold increase in the osteogenic potential of MSCs.


CONCLUSIONS
BMP-7, BMP-2, PTH, and PDGF-BB were observed to have a positive effect on osteogenic differentiation of MSCs. BMP-7 and PDGF-BB (in high doses) could be considered most potentially advantageous because they enhance both proliferation and osteogenic differentiation of MSCs derived from elderly osteoporotic bone.
Pountos
Ippokratis
I
Academic Department of Trauma & Orthopaedics, School of Medicine, University of Leeds, Leeds, UK.
Georgouli
Theodora
T
Henshaw
Karen
K
Bird
Howard
H
Jones
Elena
E
Giannoudis
Peter V
PV
D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005264:Femoral Fractures / Q000473:pathology; D050723:Fractures, Bone / Q000473:pathology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015663:Osteoporosis, Postmenopausal / Q000473:pathology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D013978:Tibial Fractures / Q000473:pathology
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D010281:Parathyroid Hormone; D010982:Platelet-Derived Growth Factor; D000469:Alkaline Phosphatase