Inflammation-induced cartilage degradation in female rodents. Protective role of sex hormones.
OBJECTIVE
To investigate the effects of physiologic levels of sex steroids on inflammation and cytokine production and their consequential cartilage degradation.


METHODS
We used an in vivo model of inflammation-induced cartilage degradation in female mice to study the effects of ovariectomy and hormone treatment, and in vitro culture systems to examine the influence of sex steroids on cartilage metabolism, interleukin-1 (IL-1) production by granulomatous tissue, and its effects on female mouse articular cartilage.


RESULTS
Ovariectomy resulted in accelerated cartilage breakdown associated with increased production of IL-1 by granulomatous tissue. The effects of ovariectomy on cartilage were reversed by treatment with estradiol and androgen, but not by progesterone treatment. Estradiol and progesterone reduced both spontaneous and IL-1-induced cartilage degradation in vitro. Testosterone antagonized the effects of IL-1 on both proteoglycan loss and proteoglycan synthesis.


CONCLUSIONS
These data suggest that sex steroids have an important influence on inflammation-induced cartilage breakdown in female animals, with protective effects of both estradiol and androgens. Multiple mechanisms may be involved, and they are likely to include direct immunomodulatory effects as well as interactions with the effects of cytokine and of the glucocorticoid response to inflammation.
da Silva
J A
JA
Department of Experimental Pathology, St. Bartholomew's Hospital Medical College, London, United Kingdom.
Colville-Nash
P
P
Spector
T D
TD
Scott
D L
DL
Willoughby
D A
DA
D000818:Animals; D002357:Cartilage Diseases / Q000209:etiology*; D002358:Cartilage, Articular / Q000737:chemistry / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology / Q000627:therapeutic use; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology / Q000627:therapeutic use*; D006099:Granuloma / Q000209:etiology / Q000378:metabolism; D007249:Inflammation / Q000503:physiopathology* / Q000517:prevention & control*; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology / Q000627:therapeutic use; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D012739:Gonadal Steroid Hormones; D007375:Interleukin-1; D011509:Proteoglycans; D013196:Dihydrotestosterone; D011374:Progesterone; D004958:Estradiol