title: Amyloid contained in the knee joint meniscus is formed from apolipoprotein A-I.
abstract: OBJECTIVE
  To determine the chemical nature of amyloid deposits found in knee joint menisci.
  
  
  METHODS
  Amyloid was extracted from the menisci of 3 adults who underwent knee joint replacement surgery. The primary structural features of the purified proteins were determined by sequential Edman degradation and tandem mass spectrometry (MS/MS). Tissue specimens were also subjected to in situ hybridization analysis, as well as complementary DNA cloning by reverse transcriptase-polymerase chain reaction (RT-PCR). Additionally, specimens from these 3 patients, as well as other patients with amyloid in the knee joint menisci, were examined immunohistochemically.
  
  
  RESULTS
  Amino acid sequence and MS/MS analyses of the extracts revealed the presence of 60-77-residue components identical to the N-terminal portion of apolipoprotein A-I (Apo A-I). The Apo A-I nature of the amyloid was confirmed by the demonstration that the green birefringent congophilic deposits in the 7 meniscus samples were recognized by an anti-human Apo A-I antibody. That the meniscus itself was the source of the amyloidogenic protein was evidenced through Southern blot analysis, in which an Apo A-I product was generated by RT-PCR from synovial tissue, and further, by the demonstration that the cytoplasm of chondrocytes reacted with the specific Apo A-I probe used for in situ hybridization and was immunostained by the anti-Apo A-I antiserum.
  
  
  CONCLUSIONS
  Amyloid in the knee joint menisci is formed from Apo A-I that is produced by chondrocytes within the meniscal cartilage. This entity represents yet another localized form of amyloidosis associated with the aging process and may be of pathophysiologic import.
authors.affiliation: University of Tennessee Center for Health Sciences, College of Medicine, Knoxville, USA. asolomon@mc.utmck.edu
authors.forename: Alan
authors.initials: A
authors.lastname: Solomon
authors.forename: Charles L
authors.initials: CL
authors.lastname: Murphy
authors.forename: Daniel
authors.initials: D
authors.lastname: Kestler
authors.forename: Daniel
authors.initials: D
authors.lastname: Coriu
authors.forename: Deborah T
authors.initials: DT
authors.lastname: Weiss
authors.forename: Josef
authors.initials: J
authors.lastname: Makovitzky
authors.forename: Per
authors.initials: P
authors.lastname: Westermark
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology*; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D003001:Cloning, Molecular; D006801:Humans; D007150:Immunohistochemistry; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology*; D008592:Menisci, Tibial / Q000378:metabolism / Q000473:pathology*; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism
chemical_list: D000682:Amyloid; D016632:Apolipoprotein A-I; D011498:Protein Precursors