Immunohistological analysis of cytokine expression in human osteoarthritic and healthy cartilage.
OBJECTIVE
To investigate osteoarthritic cartilage in comparison to normal cartilage in humans for the presence of the most relevant cytokines/growth factors known to be important for degradation and formation of new cartilage.


METHODS
Cartilage from knee or hip joints was obtained from 10 patients with osteoarthritis (OA) and from 7 age matched control patients with intact cartilage. Additionally, normal cartilage from 2 young patients (12 and 17 years old) was obtained after knee traumas. Immunohistological staining of cartilage sections was performed using antibodies for the following cytokines/growth factors: tumor necrosis factor alpha (TNF-alpha), interleukin 1alpha (IL-1alpha), IL-1beta, interferon-gamma, IL-6, IL-4, IL-10, transforming growth factor beta1 (TGF-beta1), insulin-like growth factor I (IGF-I), IGF-II, platelet derived growth factor AA (PDGF-AA), and PDGF-BB.


RESULTS
Immunohistochemical stainings were positive for all cytokines in OA cartilage, while only a faint or no staining was found in healthy cartilage. Activated chondrocytes expressing most of the cytokines were located in the middle and partly in the lower layer of cartilage, with the exception of IGF-I, which was expressed exclusively in the upper cartilage layer close to the surface. More chondrocytes stained positive for TNF-alpha than for IL-1, and expression of the degrading cytokine TNF-alpha was inversely correlated to the expression of the regulatory cytokines IL-4, IL-10, and TGF-beta.


CONCLUSIONS
The most relevant cytokines known to be involved in cartilage metabolism are produced by chondrocytes themselves. They are upregulated in OA cartilage, suggesting that they serve some regulatory function and could be a target for future treatment.
Moos
V
V
Deutsches Rheuma Forschungzentrum, Department of Medicine, Klinikum Benjamin Franklin, Free University, Berlin, Germany. hjsieper@zedat.fu-berlin.de
Fickert
S
S
Müller
B
B
Weber
U
U
Sieper
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002648:Child; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006621:Hip Joint / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D006801:Humans; D007124:Immunoenzyme Techniques; D007718:Knee Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines