Background/Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis of unknown etiology. A subset of S100 proteins known as calgranulins (S100A8, S100A9 and S100A12) are constitutively expressed at high levels in neutrophils and monocytes and play a critical role in inflammation as they can activate the innate immunity pathway sensed by Toll-like receptors. Notably, recent studies have revealed that the expression of calgranulins was about 10-fold higher in RA synovial fluid (SF) versus osteoarthritis (OA) SF. However, the mechanisms for such upregulation of the expression of calgranulins in RA SF remain unclear. We have previously demonstrated that the expression of mRNAs for various genes in BM CD34+ cells, including nuclear factor kappa B1, is higher in RA patients than in OA patients. It is thus possible that the expression of mRNAs for calgranulins might be also upregulated in RA BM CD34+ cells. The current study therefore examined the mRNA expression of S100A8, S100A9 and S100A12 in BM CD34+ cells from RA patients versus OA patients.

Methods: BM samples were obtained from 45 patients with RA (5 males and 40 females: mean age 59.0 years) and 28 patients with OA (3 males and 25 females: mean age 70.8 years), who gave informed consent, during joint operations via aspiration from iliac crest. CD34+ cells were purified from the BM mononuclear cells by positive selection with magnetic beads. The expression of mRNAs for S100A8, S100A9 and S100A12 was examined by quantitative reverse transcription PCR and is shown as the ratio of the copy numbers to those of b-actin mRNA.

Results: The expression of mRNAs for S100A9 and S100A12 was significantly higher in RA BM CD34+ cells than OA BM CD34+ cells. The expression of mRNA for S100A8 in RA BM CD34+ cells appeared to be increased compared to OA BM CD34+ cells, although it did not reach the statistical significance. (Fig. A). The mRNA expression levels of S100A8, S100A9 and S100A12 were not correlated with serum C-reactive protein or with the administration of methotrexate or oral steroid. Finally, the level of S100A8 mRNA as well as that of S100A9 mRNA was significantly correlated with the level of S100A12 mRNA in RA BM CD34+ cells (Fig. B).

Conclusion: These results indicate that the mRNA expression of S100A8, S100A9 and S100A12 is upregulated in RA BM CD34+ cells independently of the systemic inflammation or treatment regimen. Thus, the data account for the upregulation of the enhanced expression of calgranulins in RF SF compared with that in OA SF.