Quantitative determination of steroid hormone receptor positive cells in the synovium of patients with rheumatoid arthritis and osteoarthritis: is there a link to inflammation?
BACKGROUND
Steroid hormone receptors such as glucocorticoid receptors, androgen receptors, and oestrogen receptors alpha (ERalpha) and beta (ERbeta) have been identified in synovial cells of patients with rheumatoid arthritis and osteoarthritis.


OBJECTIVE
To find a quantitative relationship between the number of receptor positive cells and markers of inflammation, and to compare the two groups of patients with rheumatoid arthritis and osteoarthritis.


METHODS
A total of 36 patients with rheumatoid arthritis (n = 17) and osteoarthritis (n = 19) were included, and receptor positive cells and cellular markers of synovial inflammation were quantified by immunohistochemistry and ELISA (interleukin 6 (IL6) and IL8).


RESULTS
Patients with rheumatoid arthritis showed a higher degree of histologically determined inflammation compared with those with osteoarthritis. However, synovial density of gluco-corticoid receptor positive (GR+), androgen receptor positive (AR+), ERalpha+ and ERbeta+ cells were not different among patients with rheumatoid arthritis and osteoarthritis. In patients with osteoarthritis, the density of GR+ cells positively correlated with the density of AR+, ERalpha+ and ERbeta+ cells (p = 0.007), which was not observed in patients with rheumatoid arthritis. This indicates positively coupled steroid hormone receptor expression in patients with osteoarthritis but not in those with rheumatoid arthritis. In patients with rheumatoid arthritis, secretion of synovial IL6 and IL8 positively correlated with the density of ERalpha+ and ERbeta+ cells (not with gluco-corticoid receptor and androgen receptor), which was not found in the synovium of patients with osteoarthritis. This indicates that inflammatory factors might up regulate the expression of oestrogen receptors in patients with rheumatoid arthritis, or vice versa.


CONCLUSIONS
In patients with osteoarthritis, expression of different steroid receptors is positively coupled, which was not observed in the synovium of patients with rheumatoid arthritis. This uncoupling phenomenon in rheumatoid arthritis might lead to an imbalance of the normal synovial homeostasis.
Capellino
S
S
Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany.
Riepl
B
B
Rauch
L
L
Angele
P
P
Cutolo
M
M
Straub
R H
RH
D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D002452:Cell Count; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D047628:Estrogen Receptor alpha / Q000032:analysis; D047629:Estrogen Receptor beta / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism*; D011944:Receptors, Androgen / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000032:analysis; D011987:Receptors, Steroid / Q000032:analysis*; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000737:chemistry* / Q000276:immunology
D015415:Biomarkers; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D015850:Interleukin-6; D016209:Interleukin-8; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid