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Osteoarthritis Cartilage. 2005 Jan;13(1):66-73.

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

Author information

  • 1Rheumatology Research Laboratory, University Medical Center Nijmegen, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands.

Abstract

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.

PMID:
15639639
[PubMed - indexed for MEDLINE]
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