Amyloid contained in the knee joint meniscus is formed from apolipoprotein A-I.
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.
Solomon
Alan
A
University of Tennessee Center for Health Sciences, College of Medicine, Knoxville, USA. asolomon@mc.utmck.edu
Murphy
Charles L
CL
Kestler
Daniel
D
Coriu
Daniel
D
Weiss
Deborah T
DT
Makovitzky
Josef
J
Westermark
Per
P
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
D000682:Amyloid; D016632:Apolipoprotein A-I; D011498:Protein Precursors