title: Matrix homeostasis in aging normal human ankle cartilage.
abstract: OBJECTIVE
  To study age-related (as opposed to arthritis-related) changes in collagen and proteoglycan turnover.
  
  
  METHODS
  Macroscopically nondegenerate normal ankle cartilage obtained from 30 donors (ages 16-75 years) was processed for in situ hybridization to detect messenger RNA (mRNA) of type IIB collagen (CIIB); antibodies to the C-propeptide of type II collagen (CPII), to the type II collagen (CII) collagenase-generated cleavage neoepitope (Col2-3/4C(short)), and to the CII denaturation product (Col2-3/4m) were used for immunohistochemistry analysis and immunoassay. In addition, immunoblotting was used to detect the 4 collagenases. Assays were also performed to detect glycosaminoglycan (GAG) content and the 846 epitope of aggrecan.
  
  
  RESULTS
  There were no significant changes in CII, GAG, and the content of the 846 epitope after the age of 30 years. Both mRNA for CIIB and the CPII were present in all zones, and CPII content did not change significantly with age. While the collagenase-cleaved CII showed a trend to increase with age, the denatured collagen did not. However, the molar ratio of cleaved versus denatured collagen was positively correlated with age. All 4 collagenases were detectable in the ankle cartilage but showed no identifiable changes in content with age.
  
  
  CONCLUSIONS
  Synthesis and degradation of CII is associated with the pericellular matrix and is maintained at a steady state throughout life. The contents of CII and proteoglycan did not change. There was a significant reduction in the denaturation of CII with age, relative to collagenase-mediated cleavage. These observations reveal that, in aging of the intact ankle articular cartilage, there is no evidence of molecular degenerative changes of the kind observed in osteoarthritis, thereby distinguishing aging from the osteoarthritis process.
authors.affiliation: Department of Biochemistry, Rush Medical College at Rush-Presbyterian-St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Aurich
authors.forename: A Robin
authors.initials: AR
authors.lastname: Poole
authors.forename: Agnes
authors.initials: A
authors.lastname: Reiner
authors.forename: Christine
authors.initials: C
authors.lastname: Mollenhauer
authors.forename: Arkady
authors.initials: A
authors.lastname: Margulis
authors.forename: Klaus E
authors.initials: KE
authors.lastname: Kuettner
authors.forename: Ada A
authors.initials: AA
authors.lastname: Cole
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053674:Aggrecans; D000375:Aging / Q000378:metabolism*; D000843:Ankle Joint / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000032:analysis; D002358:Cartilage, Articular / Q000378:metabolism*; D003094:Collagen / Q000032:analysis; D024043:Collagen Type II / Q000032:analysis*; D017364:Collagenases / Q000032:analysis; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans / Q000032:analysis; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007118:Immunoassay; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D037181:Lectins, C-Type; D008875:Middle Aged; D009698:Nucleoproteins / Q000032:analysis; D011509:Proteoglycans / Q000032:analysis* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D053674:Aggrecans; D002135:Calcium-Binding Proteins; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D037181:Lectins, C-Type; D009698:Nucleoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; C040072:chondrocalcin; C090319:peptide 31D; D003094:Collagen; D017364:Collagenases