title: Increased collagen degradation around loosened total hip replacement implants.
abstract: OBJECTIVE
  To assess collagen degradation and its relationship to some of the key collagenolytic proteinases in the aggressive synovial membrane-like interface tissue around aseptically loosened hip replacement implants.
  
  
  METHODS
  The medical indication for the primary total hip replacement was osteoarthritis in all study patients. Samples from the study patients were compared with control synovial membranes obtained from trauma (hip fracture) patients. Proteoglycans were extracted with 4M guanidinium chloride. Denatured collagen in the remaining matrix was solubilized with alpha-chymotrypsin. Nonsoluble matrix and supernatant fractions were acid hydrolyzed before measurement of hydroxyproline. The proportion of soluble (in vivo-degraded) collagen of the total sample collagen content was calculated. Proteinases were stained using the avidin-biotin-peroxidase complex method.
  
  
  RESULTS
  Collagen in the interface membrane from the implants was highly degraded (mean +/- SEM 20 +/- 3%) compared with that in the control synovial membranes (12 +/- 1%; P = 0.007). In controls, the degree of collagen degradation did not correlate with levels of matrix metalloproteinase 1 (MMP-1), MMP-13, or cathepsin K, although MMP-1 approached statistical significance. In interface membranes, the correlations were r = 0.88 (P = 0.002), r = 0.92 (P = 0.001), and r = 0.98 (P < 0.0001) for MMP-1, MMP-13, and cathepsin K, respectively.
  
  
  CONCLUSIONS
  In normal synovial membrane, collagen matrix remodeling may be mainly an intracellular process. In contrast, pathologic tissue destruction in the interface membrane from prosthetic hip joints is associated with a shift toward MMP-13 and cathepsin K, which become activated and overcome their endogenous inhibitors (tissue inhibitors of metalloproteinases and cystatin C). The highly significant correlation between collagen degradation and cathepsin K indicates an extracellular role of this acidic endoproteinase, consistent with previous observations concerning the acidity of the interface membrane.
authors.affiliation: Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Ma
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ali
authors.forename: Nicole
authors.initials: N
authors.lastname: Verzijl
authors.forename: Roeland
authors.initials: R
authors.lastname: Hanemaaijer
authors.forename: Johan
authors.initials: J
authors.lastname: TeKoppele
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: Jari
authors.initials: J
authors.lastname: Salo
mesh_terms: D019644:Arthroplasty, Replacement, Hip; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D005269:Femur; D006620:Hip Fractures / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D053509:Matrix Metalloproteinase 13; D010003:Osteoarthritis / Q000378:metabolism / Q000601:surgery*; D011475:Prosthesis Failure; D012086:Reoperation; D013583:Synovial Membrane / Q000201:enzymology / Q000378:metabolism*
chemical_list: D003094:Collagen; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13