title: Expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic cartilage.
abstract: A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)1, 4, 5, 8, 9 and 15, members of the ADAMTS gene family, have the ability to degrade a major cartilage proteoglycan, aggrecan, at the specific sites, and thus are called 'aggrecanases'. The expression of these ADAMTS species was examined in human osteoarthritic articular cartilage on reverse transcription-polymerase chain reaction. The results demonstrated the predominant expression of ADAMTS4 in osteoarthritic cartilage, while ADAMTS5 was constitutively expressed in osteoarthritic and normal cartilage. ADAMTS9 was expressed mainly in normal cartilage, whereas no or negligible expression of ADAMTS1, 8 and 15 was observed in either osteoarthritic or normal cartilage. In situ hybridization for ADAMTS4 indicated that chondrocytes in osteoarthritic cartilage expressed the mRNA. Two monoclonal antibodies to ADAMTS4 were developed, and immunolocalized ADAMTS4 to chondrocytes in the proteoglycan-depleted zones of osteoarthritic cartilage, showing a direct correlation with the Mankin scores. Immunoblotting indicated a major protein band of 58 kDa in the chondrocyte culture media and osteoarthritic cartilage tissue homogenates. These data demonstrate that among the six ADAMTS species, ADAMTS4 is mainly expressed in an active form in osteoarthritic cartilage, and suggest that ADAMTS4 may play an important role in the degradation of aggrecan in human osteoarthritic cartilage.
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Tokyo.
authors.forename: Satoko
authors.initials: S
authors.lastname: Naito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shiomi
authors.forename: Aiko
authors.initials: A
authors.lastname: Okada
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Miyuki
authors.initials: M
authors.lastname: Chijiiwa
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Fujita
authors.forename: Taku
authors.initials: T
authors.lastname: Yatabe
authors.forename: Koichiro
authors.initials: K
authors.lastname: Komiya
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Enomoto
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Fujikawa
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis*; D000071121:ADAMTS4 Protein; D000368:Aged; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D010003:Osteoarthritis / Q000378:metabolism*; D011348:Procollagen N-Endopeptidase / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human