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

Pountos, Ippokratis; Georgouli, T.; Henshaw, K; Bird, H. A.; Jones, Elena; Giannoudis, Peter V.

doi:10.1097/bot.0b013e3181efa8fe

Cited by 109 publications

(92 citation statements)

References 20 publications

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“…Fortunately, PDGF as a potential drug therapy has been confirmed to enhance both proliferation and osteogenic differentiation of BMSCs derived from patients with osteoporosis. 39 PDGF-BB is a potent mitogen, 40 and the present results also suggest that the immobilized rhPDGF-BB on the nanotube surface did promote the proliferation of BMSCs from OVX rats (Supplementary Figure S4). In addition, those cells exhibited higher expression of both osteoblast-related transcription factor osterix and osteoblast-related protein OCN by stimulation by the immobilized rhPDGF-BB.…”

Section: Discussionsupporting

confidence: 49%

“…37,38 However, recent data suggest that BMSCs derived from patients with osteoporosis have a lower growth rate and osteogenic potential. 39 We tested the osteogenic differentiation ability of the BMSCs from the OVX rats. Their ALP activity and calcium deposition capacity were inferior to that of cells from the sham rats (Supplementary Figure S3).…”

Section: Discussionmentioning

confidence: 99%

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Vacuum extraction enhances rhPDGF-BB immobilization on nanotubes to improve implant osseointegration in ovariectomized rats

Zhang

Jin

Shi

et al. 2014

Nanomedicine: Nanotechnology, Biology and Medicine

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Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Vacuum extraction enhances rhPDGF-BB immobilization on nanotubes to improve implant osseointegration in ovariectomized rats

Zhang

Jin

Shi

et al. 2014

Nanomedicine: Nanotechnology, Biology and Medicine

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“…Similarly, Pountos et al observed an enhancement of proliferation and osteogenic differentiation due to BMP-2 and BMP-7 in hMSC derived from osteoporotic bone [30]. With regard to the BMP signal transduction, our group recently showed a reduced phosphorylation of ERK1/2, but an accurate activation of SMAD1/5/8 [7].…”

Section: Discussionmentioning

confidence: 89%

Mesenchymal stem cells from osteoporotic patients reveal reduced migration and invasion upon stimulation with BMP-2 or BMP-7

Haasters

Docheva

Gassner

et al. 2014

Biochemical and Biophysical Research Communications

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Fractures to the osteoporotic bone feature a delay in callus formation and reduced enchondral ossification. Human mesenchymal stem cells (hMSC), the cellular source of fracture healing, are recruited to the fracture site by cytokines, such as BMP-2 and BMP-7. Aim of the study was to scrutinize hMSC for osteoporosis associated alterations in BMP mediated migration and invasion as well as in extracellular matrix (ECM) binding integrin expression. HMSC were isolated from 18 healthy or osteoporotic donors. Migration was assessed using a collagen IV coated micro-slide linear gradient chamber and time-lapse microscopy. Invasion was analyzed utilizing an ECM coated transmembrane invasion assay. Quantitative real-time RT PCR was performed for the ECM binding integrins α1, α2, α3, α4, α5, α11, αv and β1. HMSC from osteoporotic patients showed a significant increase of migration upon BMP-2 or FCS stimulation, as well as a significant increase of invasion upon BMP-2, BMP-7 or FCS stimulation. Nevertheless, the migration and invasion capacity was significantly decreased compared to healthy controls. Out of all integrins analyzed, collagen binding integrin α2 was significantly downregulated in hMSC from osteoporotic patients. In conclusion, we here demonstrate for the first time osteoporosis associated alterations in BMP mediated hMSC recruitment. These findings may underlie the reduced healing of osteoporotic fractures. Nevertheless, the maintained migration and invasion response upon BMP stimulation illustrates the therapeutic potential of these clinically approved substances in the treatment of osteoporotic fractures. Another therapeutic target may be the downregulation of the collagen binding integrin α2 in hMSC from osteoporotic patients.

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“…Cell isolation and culture expansion was performed according to previously described methods [22][23][24][25] . Nucleated cells were isolated from the cancellous bone of the greater trochanter of fresh porcine bone obtained from the local abattoir on the day of sampling.…”

Section: Cell Isolation Cultivation and Expansionmentioning

confidence: 99%

Ability of bone graft substitutes to support the osteoprogenitor cells: Anin-vitrostudy

Dahabreh

Panteli

Pountos

et al. 2014

WJSC

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AIM:To compare seven commercially available bone graft substitutes (BGS) in terms of these properties and without using any additional biological growth factors. METHODS:Porcine osteoprogenitor cells were loaded on seven commercially available BGS and allowed to proliferate for one week followed by osteogenic induction. Staining for live/dead cells as well as scanning electron microscopy (SEM) was carried out to determine viability and cellular binding. Further outcome measures included alkaline phosphatase (ALP) assays with normalisation for DNA content to quantify osteogenic potential. Negative and positive control experiments were carried out in parallel to validate the results. RESULTS:Live/dead and SEM imaging showed higher viability and attachment with β-tricalcium phosphate (β-TCP) than with other BGS (P < 0.05). The average ALP activity in nmol/mL (normalised value for DNA content in nmol/µg DNA) per sample was 657. CONCLUSION:Under the above experimental conditions, β-TCP was able to maintain better the viability of osteoprogenitor cells and allow proliferation and differentiation (P < 0.05).© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Bone graft; Bone graft substitute; Osteoprogenitor cells; Fracture healing; Bone Core tip: Various commercially available bone graft substitutes (BGS) exist today and are used for the restoration of bone defects resulting from traumatic injury, tumor resection and congenital or degenerative diseases. Such BGS should pose osteoinductive and osteoconductive properties and support cell response to the osteogenic signalling. This study evaluated seven commercially available BGS in terms of osteoprogenitor cell adherence, proliferation and osteogenic differentiation. β-tricalcium phosphate was found to have the most favourable effect on cell viability and allow for their subsequent proliferation and differentiation.

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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

Cited by 109 publications

References 20 publications

Vacuum extraction enhances rhPDGF-BB immobilization on nanotubes to improve implant osseointegration in ovariectomized rats

Vacuum extraction enhances rhPDGF-BB immobilization on nanotubes to improve implant osseointegration in ovariectomized rats

Mesenchymal stem cells from osteoporotic patients reveal reduced migration and invasion upon stimulation with BMP-2 or BMP-7

Ability of bone graft substitutes to support the osteoprogenitor cells: Anin-vitrostudy

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