As anti-inflammatory treatments used in
rheumatoid arthritis, such as
glucocorticoids, often result in secondary detrimental effects on bone health, the objective of this study was to investigate the effects of oestrogen
therapy (ET) on the development and activity of
collagen-induced arthritis (CIA) in rats, with a focus on assessment of chondroprotective effects using
biomarkers of
type II collagen degradation. Forty female Lewis rats were allocated into four intervention groups: (i) control + vehicle; (ii) CIA + vehicle; (iii) CIA + ET; and (iv) CIA +
prednisolone. During the 28-day intervention period we monitored
body weight, time-point of disease onset, incidence of manifest disease and paw volume. Levels of the
type II collagen degradation marker (CTX-II) were measured in serum. At
euthanasia, hind paws were isolated, extracted for
proteins and measured for the concentration of CTX-II.
Matrix metalloproteinase (
MMP) activity was evaluated using
gelatinase zymography. Oestrogen
treatment delayed the time-point of disease onset and reduced the incidence and degree of manifest immunoarthritis significantly, assessed by macroscopic evaluation of hind paw
inflammation and paw volume. Measures of serum or tissue levels of CTX-II showed significantly reduced
type II collagen degradation elicited by oestrogen treatment. In alignment, a decreased activity of MMP-2 and MMP-9 was found in the paw
protein extracts. We have demonstrated that the anti-inflammatory effect of ET is linked to chondroprotective effects in an animal model of systemic immunoarthritis. As ET has positive rather than negative effects on bone health in contrast to
prednisolone, these observations may be important for potential combination
therapy.