Abstract | OBJECTIVE: To determine the proteolytic fragmentation patterns and N-terminal sequence of aggrecan fragments in human synovial fluid from patients with inflammatory arthritides, joint injury, or osteoarthritis (OA). METHODS: RESULTS: Samples from patients with joint injury, OA, and inflammatory joint disease all showed a similar 3-band pattern, with core sizes of approximately 200 kd, 170 kd, and 135 kd. In all samples, diffuse immunoreactive products were also seen, with an apparent size of > 250 kd. N-terminal analysis of core preparations of all samples showed a consistent single predominant sequence, beginning at alanine 374 of the human aggrecan core protein. CONCLUSION: The aggrecan fragments present in joint fluids from patients with various inflammatory arthritides, joint injury, or OA result from a predominant cleavage of the human aggrecan core protein at the glutamate 373-alanine 374 bond within the interglobular domain, between the G1 and G2 domains. The consistent pattern of fragments seen on SDS-PAGE and the single predominant N-terminal sequence suggest a common degradative mechanism of aggrecan in these different joint conditions. The identity of the proteolytic agent ( aggrecanase), however, remains unknown. These results appear to have important implications with regard to the development of therapies to protect cartilage from degradation in patients with joint disease.
|
Authors | L S Lohmander, P J Neame, J D Sandy |
Journal | Arthritis and rheumatism
(Arthritis Rheum)
Vol. 36
Issue 9
Pg. 1214-22
(Sep 1993)
ISSN: 0004-3591 [Print] United States |
PMID | 8216415
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Aggrecans
- Extracellular Matrix Proteins
- Lectins, C-Type
- Peptide Fragments
- Proteoglycans
- Endopeptidases
- aggrecanase
|
Topics |
- Adolescent
- Adult
- Aged
- Aggrecans
- Amino Acid Sequence
- Arthritis
(etiology)
- Blotting, Western
- Cartilage, Articular
(pathology)
- Endopeptidases
(metabolism)
- Extracellular Matrix Proteins
- Female
- Humans
- Joint Diseases
(etiology)
- Lectins, C-Type
- Male
- Middle Aged
- Molecular Sequence Data
- Osteoarthritis
(etiology)
- Peptide Fragments
(chemistry, metabolism)
- Proteoglycans
(chemistry, metabolism)
- Synovial Fluid
(metabolism)
|