Human osteocyte expression of Nerve Growth Factor: the effect of Pentosan Polysulphate Sodium (PPS) and implications for pain associated with knee osteoarthritis

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dc.contributor.authorStapledon, C.J.M.
dc.contributor.authorTsangari, H.
dc.contributor.authorSolomon, L.B.
dc.contributor.authorCampbell, D.G.
dc.contributor.authorHurtado, P.
dc.contributor.authorKrishnan, R.
dc.contributor.authorAtkins, G.J.
dc.contributor.editorHeymann, D.
dc.date.issued2019
dc.description.abstractPentosan 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.
dc.description.statementofresponsibilityCatherine J.M. Stapledon, Helen Tsangari, Lucian B. Solomon, David G. Campbell, Plinio Hurtado, Ravi Krishnan, Gerald J. Atkins
dc.identifier.citationPLoS ONE, 2019; 14(9):e0222602-1-e0222602-15
dc.identifier.doi10.1371/journal.pone.0222602
dc.identifier.issn1932-6203
dc.identifier.issn1932-6203
dc.identifier.orcidStapledon, C.J.M. [0000-0002-2827-2396]
dc.identifier.orcidTsangari, H. [0000-0001-5675-1098]
dc.identifier.orcidSolomon, L.B. [0000-0001-6254-2372]
dc.identifier.orcidCampbell, D.G. [0000-0002-1572-9529]
dc.identifier.orcidHurtado, P. [0000-0002-0913-7797]
dc.identifier.orcidAtkins, G.J. [0000-0002-3123-9861]
dc.identifier.urihttp://hdl.handle.net/2440/126219
dc.language.isoen
dc.publisherPublic Library of Science (PLoS)
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1106029
dc.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.
dc.source.urihttps://doi.org/10.1371/journal.pone.0222602
dc.subjectOsteocytes
dc.subjectHumans
dc.subjectArthralgia
dc.subjectOsteoarthritis, Knee
dc.subjectPentosan Sulfuric Polyester
dc.subjectNerve Growth Factor
dc.subjectTumor Necrosis Factor-alpha
dc.subjectAged
dc.subjectFemale
dc.subjectTranscriptome
dc.titleHuman osteocyte expression of Nerve Growth Factor: the effect of Pentosan Polysulphate Sodium (PPS) and implications for pain associated with knee osteoarthritis
dc.typeJournal article
pubs.publication-statusPublished

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