Enhanced expression of insulin-like growth factor-binding proteins in human osteoarthritic cartilage detected by immunohistochemistry and in situ hybridization.
OBJECTIVE
To determine the roles of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) in the pathogenesis of osteoarthritis (OA).


METHODS
Cartilage tissues were obtained from the femoral heads of patients with OA, and those from patients with femoral neck fractures were used as a control. The expression of IGFBP-3, -4, and -5 was examined using immunohistochemistry and in situ hybridization, and IGF-I and IGF-I receptors were also immunohistochemically detected. The percentages of positive chondrocytes were determined by counting the total number of chondrocytes over the area of the surface, middle, and deep zones of the cartilage.


RESULTS
There was a marked increase in the percentage of positive chondrocytes in all IGFBPs on protein and messenger RNA levels for OA compared to that of the control cartilage. Furthermore, enhanced expression of IGFBPs and the IGF-I/IGF-I receptor was positively correlated with the histologic score for cartilage lesions.


CONCLUSIONS
Up-regulation of IGFBPs as well as IGF-I and its receptor was observed for OA cartilage tissue, suggesting the involvement of IGFBPs in the pathogenesis of OA.
Iwanaga
Hiotoshi
H
Department of Orthopedic Surgery, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Matsumoto
Tomoko
T
Enomoto
Hiroshi
H
Okano
Kunihiko
K
Hishikawa
Yoshitaka
Y
Shindo
Hiroyuki
H
Koji
Takehiko
T
D000328:Adult; D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D019902:Chondrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000032:analysis; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000032:analysis; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000032:analysis; D013002:Somatomedins / Q000032:analysis*
D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1