OPG and RANKL in serum and synovial fluids of patients with rheumatoid arthritis, osteoarthritis and spondylarthropathy

Background

Osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) are the key regulators of osteoclastogenesis in inflammatory diseases, such as RA. OPG binds to RANKL, prevents its ligation to receptor activator of nuclear factor κB (RANK) and inhibits differentiation and activation of osteoclasts. The imbalance of this system results in the predominance of osteoresorption and bone erosions.

Objective

The aim of study was to compare the levels of OPG and soluble RANKL (sRANKL) in serum (S) and synovial fluid (SF) in rheumatoid arthritis (RA), osteoarthritis (OA) and spondylartropathies (SpA) and to correlate these levels with inflammatory parameters. We hypothesized that there is a higher local synthesis of both factors and positive correlation of sRANKL in synovial fluid with the disease activity in RA.

Methods

The paired S and knee SF samples were collected from 105 patients with RA (n = 45), OA (n = 46) and SpA (n = 14). The OPG and sRANKL levels were measured by sandwich ELISA (Biomedica).

Results

Concentrations of OPG and sRANKL were significantly higher in SF than in S in all groups (Table 1). RA and SpA groups had S-OPG and SF-OPG lower than OA. RA and OA groups differed significantly. S-sRANKL was negative in most cases in all groups. The significant negative correlation with serum CRP and SF leukocyte count was found in S-OPG, SF-OPG and SF-sRANKL.

Table 1 The mean OPG and sRANKL levels in patient cohorts

Conclusion

The increased local production of OPG and sRANKL in active joints reflects the production by inflammatory cells. Lower local and systemic concentrations of OPG in RA and SpA, but not in OA, are in agreement with the theory that OPG is insufficiently protective in inflammatory arthritis. The finding that there is no difference in SF sRANKL in RA and OA suggests that the local osteoresorption results from cell-bound RANKL rather than from the activity of the soluble form.