Establishment of treatment systematization aimed at inhibition of mandibular condyle resorption in osteoarthritis

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15390636
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthodontic/Pediatric dentistry
• Research Institution: HIROSHIMA UNIVERSITY
• Principal Investigator: TANNE Kazuo Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30159032)
• Co-Investigator(Kenkyū-buntansha): TANIMOTO Kotaro Hiroshima University, Graduate School of Biomedical Sciences, research associate, 大学院・医歯薬学総合研究科, 助手 (20322240) ; OHNO Shigeru Hiroshima University, Graduate School of Biomedical Sciences, research associate, 大学院・医歯薬学総合研究科, 助手 (30304447) ; HONDA Koubun Hiroshima University, Graduate School of Biomedical Sciences, research associate, 大学院・医歯薬学総合研究科, 助手 (00335663)
• Project Period (FY): 2003 – 2005
• Keywords: osteoarthritis / low molecular hyaluronan (HA) / synovial membrane cell / mechanical stress / hyaluronidase / chondrocyte / HAoligo / siRNA

Research Abstract

To elucidate the mechanism of cartilage degradation and pathologic progress in osteoarthritis (OA), we carried out sequential studies as follows by means of biochemical methods.
In 2003 and 2004, we examined the effects of low molecular weight hyaluronan (HA) on cultured articular chondrocytes and pursued the regulatory method for HA fragmentation. In this study, we clarified that degradation or fragmentation of HA accelerates cartilage degradation with up-regulation of matrix metalloproteinases in articular joints (Ohno-Nakahara M. et al., J.Biochem. 135 : 567-575, 2004 ; Ohno S. et al., Arthritis Rheum. 52 : 800-809, 2005). In addition, we clarified that HAS2, which played a crucial role in production of high molecular weight HA, gene expression was greatly facilitated by acting growth factor such as TGF-β on cultured synovial membrane cells (Tanimoto K. et al., J Dent.Res., 83 : 40-44, 2005).
In 2005, we examined the effects of high magnitude tensile load on HA metabolism in cultured chondrocytes and synovial membrane cells. In this study, we clarified HYAL2 gene expression and HAase activity in cultured synovial membrane cells were enhanced by high magnitude cyclic tensile load. Although HYAL2 gene expression in cultured chondrocytes was also enhanced by tensile load, HAase activity was not changed. In addition, we clarified that HYAL2 siRNA inhibited HAase activity of synovial membrane cells subjected high magnitude tensile load.
These results suggested that HA fragmentation was directly involved in cartilage degradation and the biochemical cause for HA fragmentation was HYAL2 expression induced by high magnitude tensile load. On the other hand, therefore TGF-β induced production of high molecular weight HA, it was strongly suggested that TGF-β was an effective inhibitor of cartilage degradation followed by HA fragmentation.

Research Products

• [Journal Article] Hyaluronan oligosaccharide-induced activation of transcription factors in bovine articular chondrocytes. (2005)
  • Author(s): Ohno S, Im HJ, Knudson CB, Knudson W
  • Journal Title: Arthritis Reum. 52・(3) Pages: 800-809
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The metabolism of hyaluronan in cultured rabbit growth plate chondrocytes during differentiation. (2005)
  • Author(s): Suzuki A, Tanimoto K, Ohno S, Nakatani Y, Honda K, Tanaka N, Doi T, Ohno-Nakahara M, Yoneno K, Ueki M, Tanne K
  • Journal Title: Biochim Biophys Acta 1743・(1-2) Pages: 57-63
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cyclic mechanical strain regulates the PTHrP expression in cultured chondrocytes via activation of the Ca2+ channel. (2005)
  • Author(s): Tanaka N, Ohno S, Honda K, Tanimoto K, Doi T, Ohno-Nakahara M, Tafolla E, Kapila S, Tanne K
  • Journal Title: Journal of Dental Research 84・(1) Pages: 64-68
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Hyaluronan oligosaccharide-induced activation of transcription factors in bovine articular chondrocytes. (2005)
  • Author(s): Ohno S, Im HJ, Knudson CB, Knudson W
  • Journal Title: Arthritis Reum. 52 Pages: 800-809
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The metabolism of hyaluronan in cultured rabbit growth plate chondrocytes during differentiation. (2005)
  • Author(s): Suzuki A, Tanimoto K, Ohno S, Nakatani Y, Honda K, Tanaka N, Doi T, Ohno-Nakahara M, Yoneno K, Ueki M, Tanne K
  • Journal Title: Biochim Biophys Acta 1743 Pages: 57-63
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cyclic mechanical strain regulates the PTHrP expression in cultured chondrocytes via activation of the Ca2+ channel. (2005)
  • Author(s): Tanaka N, Ohno S, Honda K, Tanimoto K, Doi T, Ohno-Nakahara M, Tafolla E, Kapila S, Tanne K
  • Journal Title: Journal of Dental Research 84 Pages: 64-68
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hyaluronidase ecpression in cultured growth plate chondrocytes during differentiation (2004)
  • Author(s): Tanimoto K, Suzuki A, Ohno S, Honda K, Tanaka N, Doi T, Nakahara-ohno M, Yoneno K, Nakatani Y, Ueki M, Yanagida T, Kitamura R, Tanne K
  • Journal Title: Cell and Tissue Research 318・(2) Pages: 335-342
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Induction of CD44 and MMP expression by hyaluronidase treatment of articular chondrocytes (2004)
  • Author(s): Nakatani Y, Ohno-Nakahara M, Honda K, Tanimoto K, Tanaka N, Doi T, Suzuki A, Nakatani Y, Ueki M, Ohno S, Knudson W,, Knudson CB, Tanne K
  • Journal Title: Journal of Biochemistry 135・(5) Pages: 567-575
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effects of TGF-beta on hyaluronan anabolism in fibroblasts derived from the synovial membrane of the rabbit temporomandibular joint. (2004)
  • Author(s): Tanimoto K, Suzuki A, Ohno S, Honda K, Tanaka N, Doi T, Yoneno K, Ohno-Nakahara M, Nakatani Y, Ueki M, Tanne K
  • Journal Title: Journal of Dental Research 83・(1) Pages: 40-44
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Hyaluronidase expression in cultured growth plate chondrocytes during differentiation. (2004)
  • Author(s): Tanimoto K, Suzuki A, Ohno S, Honda K, Tanaka N, Doi T, Nakahara-Ohno M, Yoneno K, Nakatani Y, Ueki M, Yanagida T, Kitamura R, Tanne K
  • Journal Title: Cell and Tissue Research 318 Pages: 335-342
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Induction of CD44 and MMP expression by hyaluronidase treatment of articular chondrocytes (2004)
  • Author(s): Ohno-Nakahara M, Honda K, Tanimoto K, Tanaka N, Doi T, Suzuki A, Yoneno K, Nakatani Y, Ueki M, Ohno S, Knudson W, Knudson CB, Tanne K
  • Journal Title: Journal of Biochemistry 135 Pages: 567-575
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Utility of urinary pyridinoline and deoxypyridinoline ratio for diagnosis of osteoarthritis at temporomandibular joint. (2004)
  • Author(s): Tanimoto K, Ohno S, Imada M, Honda K, Ohno-Nakahara M, Kapila S, Tanne K
  • Journal Title: J Oral Pathol Med. 33 Pages: 218-223
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effects of TGF-beta on hyaluronan anabolism in fibroblasts derived from the synovial membrane of the rabbit temporomandibular joint. (2004)
  • Author(s): Tanimoto K, Suzuki A, Ohno S, Honda K, Tanaka N, Doi T, Yoneno K, Ohno-Nakahara M, Nakatani Y. Ueki M, Tanne K
  • Journal Title: Journal of Dental Research 83 Pages: 40-44
  • Description: 「研究成果報告書概要(欧文)」より