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


Autoři: Catherine J. M. Stapledon aff001;  Helen Tsangari aff001;  Lucian B. Solomon aff001;  David G. Campbell aff001;  Plinio Hurtado aff004;  Ravi Krishnan aff005;  Gerald J. Atkins aff001
Působiště autorů: Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, South Australia, Australia aff001;  Orthopaedic and Trauma Service, Royal Adelaide Hospital, Adelaide, South Australia, Australia aff002;  Wakefield Orthopaedic Clinic, Calvary Wakefield Hospital, Adelaide, South Australia, Australia aff003;  Renal Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia aff004;  Paradigm Biopharmaceuticals Ltd., Melbourne, Victoria, Australia aff005
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222602

Souhrn

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.

Klíčová slova:

Enzyme-linked immunoassays – Gene expression – Knees – Osteoarthritis – Secretion – Osteocytes – Immunostaining – Osteoblast differentiation


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