Integrin expression on chondrocytes: correlations with the degree of cartilage damage in human osteoarthritis.
OBJECTIVE
To verify the distribution of different types of beta 1 integrin on the plasma membrane of chondrocytes and to correlate the pattern of integrin expression to the severity of osteoarthritis (OA).


METHODS
The articular cartilage of ten OA patients who had undergone surgical knee replacement for "genu varum" were studied. The cartilage was separated into three zones that macroscopically and microscopically showed a decreasing degree of anatomic lesions. After enzymatic digestion, the isolated chondrocytes were immediately challenged with monoclonal antibodies against the beta 1, alpha 1-6 and alpha v chains. The phenotypic study was paralleled by a cell cycle analysis performed by flow cytometry on chondrocytes stained with propidium iodide.


RESULTS
Chondrocytes isolated from the articular cartilage of osteoarthritic patients expressed, in different percentages, all the alpha chains (alpha 1-6 and alpha v) of the beta 1 integrins. The alpha chain most frequently expressed was alpha 1, followed by alpha 3, alpha 5, alpha 2 and alpha v, with lesser amounts of alpha 4 and alpha 6. The beta 1 chain was expressed (on average) on the 40% of the chondrocytes regardless of the zone they were isolated from. Differential phenotypic analysis of the three zones showed that beta 1 integrins correlate inversely with the severity of the anatomic lesions and the cycle phase of the chondrocytes (the G0/G1 phase prevailed in the anatomically normal cartilage of the least damaged zone, and the S-phase in the most damaged zone).


CONCLUSIONS
This study provides evidence of the existence of beta 1 integrins on the surface of chondrocytes from human OA cartilage, all of the alpha chains being represented, although in different percentages. Moreover, an inverse correlation was demonstrated between the severity of the anatomical changes found in the zones and the phenotypic/metabolic changes of the cells. These results, together with the well known inside-out signaling function of the adhesion molecules, highlight the key role of matrix interactions in the pathogenesis of the anatomic changes in OA.
Lapadula
G
G
Cattedra di Reumatologia, Università degli Studi di Bari, Italy.
Iannone
F
F
Zuccaro
C
C
Grattagliano
V
V
Covelli
M
M
Patella
V
V
Lo Bianco
G
G
Pipitone
V
V
D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle; D005260:Female; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology*
D016023:Integrins