Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/126219
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Type: Journal article
Title: Human osteocyte expression of Nerve Growth Factor: the effect of Pentosan Polysulphate Sodium (PPS) and implications for pain associated with knee osteoarthritis
Author: Stapledon, C.J.M.
Tsangari, H.
Solomon, L.B.
Campbell, D.G.
Hurtado, P.
Krishnan, R.
Atkins, G.J.
Citation: PLoS ONE, 2019; 14(9):e0222602-1-e0222602-15
Publisher: Public Library of Science (PLoS)
Issue Date: 2019
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Catherine J.M. Stapledon, Helen Tsangari, Lucian B. Solomon, David G. Campbell, Plinio Hurtado, Ravi Krishnan, Gerald J. Atkins
Abstract: Pentosan polysulphate sodium (PPS) is a promising therapeutic agent for blocking knee pain in individuals with knee osteoarthritis (KOA). The mode of action of PPS in this context is unknown. We hypothesised that the osteocyte, being the principal cell type in the sub-chondral bone, was capable of expressing the pain mediator Nerve Growth Factor (NGF), and that this may be altered in the presence of PPS. We tested the expression of NGF and the response to PPS in the presence or absence of the proinflammatory cytokine tumour necrosis factor-alpha (TNFα), in human osteocytes. For this we differentiated human primary osteoblasts grown from subchondral bone obtained at primary knee arthroplasty for KOA to an osteocyte-like stage over 28d. We also tested NGF expression in fresh osteocytes obtained by sequential digestion from KOA bone and by immunofluorescence in KOA bone sections. We demonstrate for the first time the production and secretion of NGF/proNGF by this cell type derived from patients with KOA, implicating osteocytes in the pain response in this pathological condition and possibly others. PPS inhibited TNFα-induced levels of proNGF secretion and TNFα induced NGF mRNA expression. Together, this provides evidence that PPS may act to suppress the release of NGF in the subchondral bone to ameliorate pain associated with knee osteoarthritis.
Keywords: Osteocytes; Humans; Arthralgia; Osteoarthritis, Knee; Pentosan Sulfuric Polyester; Nerve Growth Factor; Tumor Necrosis Factor-alpha; Aged; Female; Transcriptome
Rights: © 2019 Stapledon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 1000001316
DOI: 10.1371/journal.pone.0222602
Grant ID: http://purl.org/au-research/grants/nhmrc/1106029
Appears in Collections:Medicine publications

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