title: Induction of CD44 and MMP expression by hyaluronidase treatment of articular chondrocytes.
abstract: In this study, the effects of fragmentation of the glycosoaminoglycans of the cell-associated matrix by hyaluronidase (HAase) on the expression of CD44 receptor and matrix metalloproteinase (MMP) mRNAs in cultured articular chondrocytes were examined. Chondrocytes, isolated from rabbit and bovine articular cartilage, were treated with bovine testicular HAase (0-200 units/ml) in the presence or absence of an antibody for CD44. The mRNA levels of CD44, CD44 variant (CD44v), MMPs (MMP-1, -3 and -9), and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were determined by RT-PCR. The treatment of cultured chondrocytes with HAase resulted in the production of low molecular weight fragments of hyaluronan (HA). The expression of CD44, CD44v and MMP (MMP-1, -3 and -9) mRNAs, but not TIMP-1 or TIMP-2 mRNA, was up-regulated in the cultures treated with HAase, whereas this expression was not affected by treatment with purified HA of 1.0 x 10(5) Da. Furthermore, the induction of CD44 and MMPs on treatment with HAase was suppressed by an anti-CD44 antibody. The results suggest that the fragmentation of HA may lead to cartilage destruction in terms of the enhanced expression of MMPs as well as the upregulation of CD44.
authors.affiliation: Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553.
authors.forename: Maiko
authors.initials: M
authors.lastname: Ohno-Nakahara
authors.forename: Kobun
authors.initials: K
authors.lastname: Honda
authors.forename: Kotaro
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Doi
authors.forename: Aya
authors.initials: A
authors.lastname: Suzuki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoneno
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ohno
authors.forename: Warren
authors.initials: W
authors.lastname: Knudson
authors.forename: Cheryl B
authors.initials: CB
authors.lastname: Knudson
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tanne
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004586:Electrophoresis; D005786:Gene Expression Regulation; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D006821:Hyaluronoglucosaminidase; D020782:Matrix Metalloproteinases