Induction of CD44 and MMP expression by hyaluronidase treatment of articular chondrocytes.
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.
Ohno-Nakahara
Maiko
M
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553.
Honda
Kobun
K
Tanimoto
Kotaro
K
Tanaka
Nobuaki
N
Doi
Takeyoshi
T
Suzuki
Aya
A
Yoneno
Kiyoshi
K
Nakatani
Yuki
Y
Ueki
Masashi
M
Ohno
Shigeru
S
Knudson
Warren
W
Knudson
Cheryl B
CB
Tanne
Kazuo
K
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
D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D006821:Hyaluronoglucosaminidase; D020782:Matrix Metalloproteinases