title: Tissue inhibitor of metalloproteinase 1, collagenolytic and gelatinolytic activity in loose hip endoprostheses.
abstract: OBJECTIVE
  To study tissue inhibitor of metalloproteinase 1 (TIMP-1) in relation to collagenolytic and gelatinolytic potential, namely dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg (DNP-S) sensitive proteolytic activity, in loose total hip arthroplasty (THA) endoprostheses.
  
  
  METHODS
  Tissue localization of TIMP-1 was investigated immunohistochemically. TIMP-1 level of the periprosthetic tissues and fluid samples from 9 loose THA endoprostheses was measured by competitive ELISA, and DNP-S sensitive collagenolytic and gelatinolytic potential was evaluated by the degradation of synthetic DNP-S and reverse phase high performance liquid chromatography.
  
  
  RESULTS
  Immunohistochemical analysis revealed moderate to marked immunoreactivity of TIMP-1 in pseudosynovial lining cells, and weak to moderate immunoreactivity often in monocyte/macrophages, endothelial cells, and fibroblasts in both interface tissues between bone and implant and pseudocapsular tissues around the artificial joints. TIMP-1 level was low in interface tissue samples (795 +/- 203 ng/ml) compared to pseudosynovial fluid samples (2026 +/- 584 ng/ml). Degradation rate of the substrate was higher in interface tissue samples (56 +/- 6%) than in pseudocapsular tissue samples (32 +/- 4%) and pseudosynovial fluid samples (6 +/- 2%).
  
  
  CONCLUSIONS
  Low TIMP-1 level combined with high percentage of degradation of synthetic substrate DNP-S leads to high collagenolytic and gelatinolytic activity in interface tissue samples. This may in part explain the weakening of periprosthetic connective tissue. Weakening combined with cyclic mechanical loading may lead to loosening of THA endoprostheses.
authors.affiliation: Institute of Biomedicine and the Institute of Dentistry, University of Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Takagi
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: P
authors.initials: P
authors.lastname: Kemppinen
authors.forename: T
authors.initials: T
authors.lastname: Sorsa
authors.forename: H
authors.initials: H
authors.lastname: Tschesche
authors.forename: J
authors.initials: J
authors.lastname: Bläser
authors.forename: A
authors.initials: A
authors.lastname: Suda
authors.forename: S
authors.initials: S
authors.lastname: Santavirta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001672:Biocompatible Materials; D002851:Chromatography, High Pressure Liquid; D003094:Collagen / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005780:Gelatin / Q000378:metabolism*; D006023:Glycoproteins / Q000032:analysis*; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011475:Prosthesis Failure; D011480:Protease Inhibitors / Q000032:analysis*; D018709:Statistics, Nonparametric; D013582:Synovial Fluid / Q000737:chemistry; D013583:Synovial Membrane / Q000737:chemistry; D014018:Tissue Distribution; D019714:Tissue Inhibitor of Metalloproteinases
chemical_list: D001672:Biocompatible Materials; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D005780:Gelatin; D003094:Collagen