Male IL-6 gene knock out mice developed more advanced osteoarthritis upon aging

Osteoarthritis Cartilage. 2005 Jan;13(1):66-73. doi: 10.1016/j.joca.2004.09.011.


Objective: Interleukin-6 (IL-6) is expressed in osteoarthritic joints but its function in osteoarthritis (OA) is unknown. To study this, spontaneous and experimental OA were evaluated in IL-6 deficient (IL-6(-/-)) mice.

Design: Histology of knees of 18-23-month-old wild type (wt) and IL-6(-/-) mice was compared for signs of OA. Cartilage proteoglycan (PG) density was measured by image analysis on safranin-O stained whole knee sections. Chondrocyte PG synthesis was measured ex vivo by (35)S-sulfate incorporation. Knee bone mineral density (BMD) was measured by dual energy x-ray absorptiometry. In young mice (3 months), OA was induced by intra-articular injection of collagenase.

Results: The incidence of extensive cartilage loss at both lateral and medial sides was markedly higher in old IL-6(-/-) males, but not in females, as compared to their wt controls. Compared to age-matched wt mice, reduced ex vivo PG synthesis was found during aging in IL-6(-/-) males, without affecting their cartilage PG density. IL-6(-/-) males showed more extensive extracellular matrix deposition in the collateral ligaments and subchondral bone sclerosis, predominantly at the medial side. Total knee BMD decreased more in IL-6(-/-) (-23%) than in wt (-10%) males during aging. Collagenase-induced OA showed a similar degree of joint pathology in both strains, implying that OA susceptibility was not different at younger age.

Conclusions: Upon aging, IL-6(-/-) male mice developed more severe spontaneous OA. Reduced PG synthesis and BMD values might be indicative for an impaired repair response in IL-6(-/-) mice. This suggests a protective role for IL-6 in age-related OA in male mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology*
  • Aging / physiology
  • Animals
  • Arthritis, Experimental / genetics
  • Arthritis, Experimental / pathology*
  • Arthritis, Experimental / physiopathology
  • Bone Density
  • Cartilage, Articular / pathology
  • Chondrocytes / metabolism
  • Collagenases
  • Female
  • Interleukin-6 / deficiency
  • Interleukin-6 / genetics
  • Interleukin-6 / physiology*
  • Ligaments / metabolism
  • Ligaments / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Osteoarthritis / genetics
  • Osteoarthritis / pathology*
  • Osteoarthritis / physiopathology
  • Prostaglandins / biosynthesis
  • Sclerosis
  • Sex Factors
  • Tibia / pathology


  • Interleukin-6
  • Prostaglandins
  • Collagenases