Expression of membrane-bound peptidases (CD10 and CD26) on human articular chondrocytes. Possible role of neuropeptidases in the pathogenesis of osteoarthritis.
OBJECTIVE
To evaluate the cell surface expression of cell membrane-bound peptidases CD10 and CD26 on osteoarthritic (OA) chondrocytes, correlating it with the cell cycle phase and with the severity of OA lesions found in different load zones of the cartilage from human knees.


METHODS
Chondrocytes freshly isolated from three different load zones of cartilage, obtained from 10 OA patients undergoing surgical knee replacement, were analyzed for the expression of CD10 and CD26 and for their cell cycle phase by flow cytometry. Statistical analysis was carried out using the multifactorial analysis of the variance with the LSD (least square difference) range test. The Chi square test was used to compare the cell cycle phases.


RESULTS
Analysis of the chondrocyte cell cycle showed a significantly high proportion of cells in the S-phase in the maximum load zone in comparison with the minimum load zone (p < 0.001); the percentage of resting cells (G0/G1 phase) was significantly higher in the minimum load zone than in the maximum load zone (p < 0.001). The expression of CD10 and CD26 on chondrocytes was significantly reduced in the maximum load zone of the cartilage and was directly related to the progressive worsening of osteoarthritic lesions.


CONCLUSIONS
These data demonstrate, for the first time, that articular chondrocytes express on their surface CD10 and CD26 peptidases. Neprilysin 3.4.24.11 (CD10) and dipeptidyl peptidase IV 3.4.14.15 (CD26) have been shown to play a specific role in the control of growth and differentiation of many cell types by cleaving growth factors able to promote cellular proliferation. Our results indicate that CD10 and CD26 are down-regulated in the maximum load zone of the knee OA cartilage: this condition may allow the increase of local levels of growth factors causing chondrocyte activation. Furthermore, as CD26 mediates cell binding to fibronectin and collagen, its reduction in osteoarthritic cartilage may reflect a perturbation of chondrocyte interactions with the extracellular matrix.
Lapadula
G
G
Cattedra di Reumatologia, Università degli Studi di Bari, Italy.
Iannone
F
F
Zuccaro
C
C
Covelli
M
M
Patella
V
V
Lobianco
G
G
Pipitone
V
V
D000368:Aged; D002358:Cartilage, Articular / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D002453:Cell Cycle; D002462:Cell Membrane / Q000201:enzymology / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015260:Neprilysin / Q000378:metabolism*; D010003:Osteoarthritis / Q000201:enzymology* / Q000209:etiology / Q000473:pathology
D018819:Dipeptidyl Peptidase 4; D015260:Neprilysin