Unbalanced levels of bone resorption promoting factors in bone marrow from patients with rheumatoid arthritis in comparison to osteoarthritis

Introduction

RANKL and IL-6 participate in osteoclast differentiation and activation, and therefore regulate bone resorption. The biological activity of RANKL is inhibited by its natural decoy receptor osteoprotegerin (OPG), while IL-6 activity is either enhanced by soluble IL-6 receptor (sIL-6R) or inhibited by soluble glycoprotein 130 (sgp130), an extracellular domain of the signaling chain of the IL-6 receptor complex.

Objectives

To compare the levels of RANKL, OPG, IL-6, sIL-6R and sgp130 in bone marrow plasma isolated from rheumatoid arthritis (RA) and osteoarthritis (OA) patients.

Methods

Bone marrow samples isolated from 29 RA patients and 12 OA patients (mean age 51 ± 14.3 years and 56.3 ± 10.5 years, respectively) undergoing hip replacement surgery were diluted twice in heparinized PBS. The levels of cytokines were measured using specific ELISAs.

Results

The levels of tested cytokines, the ratio of respective ligands to their receptors and the statistical significance of the data are presented in Table 1.

Table 1 Levels of RANKL, osteoprotegerin (OPG), IL-6, soluble IL-6 receptor (sIL-6R), and soluble glycoprotein 130 (sgp130) in the bone marrow of rheumatoid arthritis and osteoarthritis patients

The levels of RANKL in RA patients were elevated by 53% in comparison with those in OA patients. In contrast, the levels of OPG were diminished by 20%. Thus, the ratio of OPG/RANKL, thought to better reflect environmental signals promoting bone resorption than levels of individual cytokines, is diminished in RA patients in comparison with OA patients. Similarly, the 115% increase of IL-6 and the 102% increase of sIL-6R is not compensated for by only the 59% increase of sgp130 in RA patients in comparison with OA patients.

Conclusion

The present data indicate that the bone marrow microenvironment of RA patients in comparison with OA patients is enriched in factors promoting osteoclastogenesis, osteoclast activation and bone resorption. At the same time, the levels of corresponding natural decoy receptors is diminished. Thus, RA-associated osteoporosis and bone erosions may, at least partially, be related to unbalanced production of RANKL, IL-6 and sIL-6R in the bone marrow.