Induction of CD44 and MMP Expression by Hyaluronidase Treatment of Articular Chondrocytes

Maiko Ohno-Nakahara; Kobun Honda; Kotaro Tanimoto; Nobuaki Tanaka; Takeyoshi Doi; Aya Suzuki; Kiyoshi Yoneno; Yuki Nakatani; Masashi Ueki; Shigeru Ohno; Warren Knudson; Cheryl B. Knudson; Kazuo Tanne

doi:10.1093/jb/mvh069

Maiko Ohno-Nakahara, Kobun Honda, Kotaro Tanimoto, Nobuaki Tanaka, Takeyoshi Doi, Aya Suzuki, Kiyoshi Yoneno, Yuki Nakatani, Masashi Ueki, Shigeru Ohno, Warren Knudson, Cheryl B. Knudson, Kazuo Tanne

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Maiko Ohno-Nakahara
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences
Department of Biochemistry, Rush Medical College, Rush University Medical Center
Kobun Honda
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences
Kotaro Tanimoto
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences
Nobuaki Tanaka
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences
Takeyoshi Doi
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences
Aya Suzuki
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences
Kiyoshi Yoneno
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences
Yuki Nakatani
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences
Masashi Ueki
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences
Shigeru Ohno
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences
Department of Biochemistry, Rush Medical College, Rush University Medical Center
Warren Knudson
Department of Biochemistry, Rush Medical College, Rush University Medical Center
Cheryl B. Knudson
Department of Biochemistry, Rush Medical College, Rush University Medical Center
Kazuo Tanne
Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences

Keywords: CD44, chondrocytes, hyaluronan, hyaluronidase, matrix metalloproteinase (MMP)

JOURNAL FREE ACCESS

2004 Volume 135 Issue 5 Pages 567-575

DOI https://doi.org/10.1093/jb/mvh069

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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 1.0×10⁵ 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.

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