Distribution and role of tenascin-C in human osteoarthritic cartilage.
BACKGROUND
Tenascin-C (TN-C) is expressed in the cartilage of osteoarthritis (OA). We examined whether TN-C was involved in cartilage repair of the diseased joints. Human articular cartilage samples were obtained from patients with OA and those with normal joints.


METHODS
Immunohistochemistry testing of TN-C, chondroitin sulfate (CS), and proliferating cell nuclear antigen (PCNA) was performed. Chondrocytes were isolated from human cartilage and cultured. After treatment with TN-C, chondrocyte proliferation s was analyzed by bromodeoxyuridine (BrdU) incorporation assay using an enzyme-linked immunosorbent assay kit. Glycosaminoglycan content was determined by dimethylmethylene blue (DMMB) assay. The mRNA expression of aggrecan was also analyzed, by quantitative real-time polymerase chain reaction (PCR).


RESULTS
In osteoarthritic cartilage, increased TN-C staining was observed with the degeneration of articular cartilage in comparison with normal cartilage. TN-C staining was shown in the cartilage surface overlying CS-positive areas. In addition, the expression of PCNA in the positive areas for TN-C was significantly higher than that in the negative areas. Treatment of human articular chondrocytes with 10 μg/ml TN-C accelerated chondrocyte proliferation, increased the proteoglycan amount in culture, and increased the expression of aggrecan mRNA.


CONCLUSIONS
Our findings indicate that the distribution of TN-C is related to CS production and chondrocyte proliferation in osteoarthritic cartilage and that TN-C has effects on DNA synthesis, proteoglycan content, and aggrecan mRNA expression in vitro. TN-C may be responsible for repair in human osteoarthritic cartilage.
Department of Orthopedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, Mie 514-8507, Japan.
Yutaka
Y
Nakoshi
Masahiro
M
Hasegawa
Koji
K
Akeda
Takahiro
T
Iino
Akihiro
A
Sudo
Toshimichi
T
Yoshida
Atsumasa
A
Uchida
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D002809:Chondroitin Sulfates / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007719:Knee Joint; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism* / Q000494:pharmacology; D055815:Young Adult
D018809:Proliferating Cell Nuclear Antigen; D019063:Tenascin; D002809:Chondroitin Sulfates