title: Male IL-6 gene knock out mice developed more advanced osteoarthritis upon aging.
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.
  
  
  METHODS
  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.
authors.affiliation: Rheumatology Research Laboratory, University Medical Center Nijmegen, Nijmegen Center for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Alfons S K
authors.initials: AS
authors.lastname: de Hooge
authors.forename: Fons A J
authors.initials: FA
authors.lastname: van de Loo
authors.forename: Miranda B
authors.initials: MB
authors.lastname: Bennink
authors.forename: Onno J
authors.initials: OJ
authors.lastname: Arntz
authors.forename: Pieter
authors.initials: P
authors.lastname: de Hooge
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D015519:Bone Density; D002358:Cartilage, Articular / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism; D017364:Collagenases; D005260:Female; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008022:Ligaments / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D011453:Prostaglandins / Q000096:biosynthesis; D012598:Sclerosis; D012737:Sex Factors; D013977:Tibia / Q000473:pathology
chemical_list: D015850:Interleukin-6; D011453:Prostaglandins; D017364:Collagenases