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

Stapledon CJM, Tsangari H, Solomon LB, Campbell DG, Hurtado P, Krishnan R, Atkins GJ · PLoS One

The proposed pain mechanism, shown in human OA tissue for the first time: osteocytes in arthritic subchondral bone make and secrete nerve growth factor, and PPS reduced both the cytokine-driven secretion of its precursor and NGF messenger-RNA induction. Nerve growth factor is the target of the anti-NGF analgesics, which makes this a plausible route to symptom relief that is not structural.

Population

Osteocyte-like cells differentiated from subchondral bone taken at knee replacement for osteoarthritis, plus fresh osteocytes and bone sections

Intervention

PPS, with and without tumour necrosis factor-α

Comparator

Untreated and cytokine-only cultures

Limitations

Cultured cells from three arthroplasty donors, all women around 77, plus fracture controls; no dose-response, which the authors call a limitation. Funded by a Paradigm research grant and an NHMRC grant; one author is a Paradigm employee with incentive compensation and the company has filed patents on treating pain with polysulfated polysaccharides.