Sex differences in inflammation induced cartilage damage in rodents. The influence of sex steroids

J Rheumatol. 1994 Feb;21(2):330-7.


Objective: To investigate sex differences in granulomatous inflammation and its effects upon articular cartilage and to assess the potential role of sex steroids in the process.

Methods: The cotton-pellet cartilage implant model was used with male and female mice in the presence and absence of gonadectomy and hormone replacement. The effects of granulomatous tissue upon articular cartilage was assessed and tissue content of interleukin 1 (IL-1) was determined. The expression of sex hormone receptors in inflammatory tissue was investigated by immunocytochemistry.

Results: Female mice showed a higher ability than males to degrade cartilage irrespective of the sex of the cartilage implanted. Gonadectomy resulted in a significant acceleration of cartilage damage in both sexes, which was reverted by estrogen replacement in females and androgen replacement in males. Female granulomata had significantly higher IL-1 content than those from males. Gonadectomy was associated with an increased IL-1 content in males but not in females, the effects being abolished by androgen replacement in males. Estrogen and androgen receptors were identified in inflammatory cells from the granulomatous tissue.

Conclusion: Our data demonstrate that sex hormones affect inflammation induced cartilage degradation in male and female mice probably through the modulation of cytokine production and release in the granulomatous tissue. Further investigation on the effects of sex steroids in inflammation induced cartilage degradation may help elucidate their pathogenic role and therapeutic potential in human disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis / etiology*
  • Arthritis / pathology
  • Arthritis / physiopathology
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / pathology*
  • Cartilage, Articular / physiopathology
  • Dihydrotestosterone / pharmacology
  • Disease Models, Animal
  • Estradiol / pharmacology
  • Female
  • Gonadal Steroid Hormones / physiology*
  • Granuloma / pathology
  • Granuloma / physiopathology
  • Interleukin-1 / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Androgen / metabolism
  • Receptors, Estrogen / metabolism
  • Sex Characteristics


  • Gonadal Steroid Hormones
  • Interleukin-1
  • Receptors, Androgen
  • Receptors, Estrogen
  • Dihydrotestosterone
  • Estradiol