Published online May 20, 2017. doi: 10.5493/wjem.v7.i2.49
Peer-review started: February 8, 2017
First decision: March 8, 2017
Revised: April 26, 2017
Accepted: May 3, 2017
Article in press: May 5, 2017
Published online: May 20, 2017
To characterise the role of substitutes for receptor-activator nuclear factor kappa-B ligand (RANKL) in rheumatoid arthritis (RA) joint destruction.
Synovial fluid (SF) macrophages isolated from the knee joint of RA patients were incubated with 25 ng/mL macrophage-colony stimulating factor (M-CSF) and 50 ng/mL LIGHT (lymphotoxin-like, exhibits inducible expression and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes) in the presence and absence of 25 ng/mL RANKL and 100 ng/mL osteoprotegerin (OPG) on glass coverslips and dentine slices. Osteoclastogenesis was assessed by the formation of multinucleated cells (MNCs) expressing tartrate-resistant acid phosphatase (TRAP) on coverslips and the extent of lacunar resorption pit formation on dentine slices. The concentration of LIGHT in RA and osteoarthritis (OA) synovial fluid was measured by an enzyme-linked immunosorbent assay (ELISA) and the expression of LIGHT in RA and OA synovium was determined by immunohistochemistry using an indirect immunoperoxidase technique.
In cultures of RA SF macrophages treated with LIGHT and M-CSF, there was significant formation of TRAP + MNCs on coverslips and extensive lacunar resorption pit formation on dentine slices. SF-macrophage-osteoclast differentiation was not inhibited by the addition of OPG, a decoy receptor for RANKL. Resorption pits were smaller and less confluent than in RANKL-treated cultures but the overall percentage area of the dentine slice resorbed was comparable in LIGHT- and RANKL-treated cultures. LIGHT significantly stimulated RANKL-induced lacunar resorption compared with RA SF macrophages treated with either RANKL or LIGHT alone. LIGHT was strongly expressed by synovial lining cells, subintimal macrophages and endothelial cells in RA synovium and the concentration of LIGHT was much higher in RA compared with OA SF.
LIGHT is highly expressed in RA synovium and SF, stimulates RANKL-independent/dependent osteoclastogenesis from SF macrophages and may contribute to marginal erosion formation.
Core tip: Rheumatoid arthritis (RA) is an inflammatory joint condition characterised by the formation of marginal erosions due to the activity of bone resorbing osteoclasts. Osteoclasts can be formed from macrophages by both receptor-activator nuclear factor kappa-B ligand (RANKL)-dependent and RANKL-independent mechanisms. LIGHT is a potent RANKL substitute that induces significant osteoclast formation from cultures of RA synovial fluid macrophages; this results in comparable levels of resorption to that seen in RANKL-treated cultures. LIGHT also stimulated RANKL-mediated lacunar resorption. LIGHT is highly expressed in RA joints and synovial fluid and is likely to play a key role in the pathogenesis of marginal erosion formation in RA.