PLoS One. 2016 Oct 4;11(10):e0163530. doi: 10.1371/journal.pone.0163530. eCollection 2016.
Pyrophosphate Stimulates Differentiation, Matrix Gene Expression and Alkaline Phosphatase Activity in Osteoblasts.
Pujari-Palmer M1, Pujari-Palmer S1, Lu X1, Lind T2, Melhus H2, Engstrand T3,4, Karlsson-Ott M1, Engqvist H1.
Abstract
Pyrophosphate
is a potent mitogen, capable of stimulating proliferation in multiple
cell types, and a critical participant in bone mineralization.
Pyrophosphate can also affect the resorption rate and bioactivity of
orthopedic ceramics. The present study investigated whether calcium
pyrophosphate affected proliferation, differentiation and gene
expression in early (MC3T3 pre-osteoblast) and late stage (SAOS-2
osteosarcoma) osteoblasts. Pyrophosphate stimulated peak alkaline
phosphatase activity by 50% and 150% at 100μM and 0.1μM in MC3T3, and by
40% in SAOS-2. The expression of differentiation markers collagen 1
(COL1), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin
(OCN) were increased by an average of 1.5, 2, 2 and 3 fold, by high
concentrations of sodium pyrophosphate (100μM) after 7 days of exposure
in MC3T3. COX-2 and ANK expression did not differ significantly from
controls in either treatment group. Though both high and low
concentrations of pyrophosphate stimulate ALP activity, only high
concentrations (100μM) stimulated osteogenic gene expression.
Pyrophosphate did not affect proliferation in either cell type. The
results of this study confirm that chronic exposure to pyrophosphate
exerts a physiological effect upon osteoblast differentiation and ALP
activity, specifically by stimulating osteoblast differentiation markers
and extracellular matrix gene expression.
- PMID:
- 27701417
- DOI:
- 10.1371/journal.pone.0163530
- [PubMed - in process]
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