Expression analysis of three isoforms of hyaluronan synthase and hyaluronidase in the synovium of knees in osteoarthritis and rheumatoid arthritis by quantitative real-time reverse transcriptase polymerase chain reaction

Arthritis Research & Therapy

Mamoru Yoshida¹  Shigaku Sai¹  Keishi Marumo¹  Takaaki Tanaka¹  Naoki Itano²  Koji Kimata²  Katsuyuki Fujii¹ 

[1] Department of Orthopaedic Surgery, The Jikei University School of Medicine, Tokyo, Japan

[2] Institute for Molecular Science of Medicine, Aichi Medical University, Aichi, Japan

关键词: synovium;    hyaluronidase;    hyaluronan synthase;    hyaluronan;    arthritis;   

Others  :  1101206
DOI  :  10.1186/ar1223

 received in 2003-10-02, accepted in 2004-07-16,  发布年份 2004

【 摘 要 】

Hyaluronan is a major molecule in joint fluid and plays a crucial role in joint motion and the maintenance of joint homeostasis. The concentration and average molecular weight of hyaluronan in the joint fluids are reduced in osteoarthritis and rheumatoid arthritis. To elucidate the underlying mechanism, we analyzed the message expression of three isoforms of hyaluronan synthase and hyaluronidase from knee synovium, using real-time reverse transcriptase polymerase chain reaction. Synovia were obtained from 17 patients with osteoarthritis, 14 patients with rheumatoid arthritis, and 20 healthy control donors. The message expression of hyaluronan synthase-1 and -2 in the synovium of both types of arthritis was significantly less than in the control synovium, whereas that of hyaluronidase-2 in the synovium of both arthritides was significantly greater than in the control synovium. The decreased expression of the messages for hyaluronan synthase-1 and -2 and/or the increased expression of the message for hyaluronidase-2 may be reflected in the reduced concentration and decreased average molecular weight of hyaluronan in the joint fluids of patients with osteoarthritis and rheumatoid arthritis.

【 授权许可】

   
2004 Yoshida et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Saari H, Kontinen YT: Determination of the concentration and polymerization of synovial fluid hyaluronate using high performance liquid chromatography. Ann Rheum Dis 1989, 48:565-570.
• [2]Balazs EA, Denlinger JL: Viscosupplementation: a new concept in the treatment of osteoarthritis. J Rheumatol 1993, Suppl 39:3-9.
• [3]Ghosh P: The role of hyaluronic acid (hyaluronan) in health and disease: interactions with cells, cartilage and components of the synovial fluid. Clin Exp Rheumatol 1994, 12:75-82.
• [4]Abatangelo G, O'Regan M: Hyaluronan: biological role and function in articular joints. Eur J Rheumatol Inflamm 1995, 15:9-16.
• [5]Laurent TC, Laurent UBG, Fraser JRE: The structure of hyaluronan: an overview. Immunol Cell Biol 1996, 74:A1-7.
• [6]Brandt KD, Smith GN Jr, Simon LS: Intraarticular injection of hyaluronan as treatment for knee osteoarthritis. What is the evidence? [review]. Arthritis Rheum 2000, 43:1192-1203.
• [7]Yasui Y, Akatsuka M, Tobetto K, Hayaishi M, Ando T: The effects of hyaluronan on interleukin-1 alpha-induced prostaglandin E2 production in human osteoarthritic synovial cells. Agents Actions 1992, 37:155-156.
• [8]Tobetto K, Yasui T, Ando T: Inhibition effect of hyaluronan on 14C arachidonic acid release from labeled human synovial fibroblasts. Jpn J Pharmacol 1992, 60:79-84.
• [9]Larsen NE, Lombard KM, Parent EG, Balazs EA: Effect of hylan on cartilage and chondrocyte cultures. J Orthop Res 1992, 10:23-32.
• [10]Presti D, Scott JE: Hyaluronan mediated protective effect against cell damage caused by enzymatically generated hydroxyl radicals is dependent on hyaluronan molecular mass. Cell Biochem Funct 1994, 12:281-288.
• [11]Balazs EA, Briller S, Denlinger JL: Na-hyaluronate molecular size variations in equine and arthritic synovial fluid and effect on phagocytic cells. Semin Arthritis Rheum 1981, 11:141-143.
• [12]Forrester JV, Balazs EA: Inhibition of phagocytosis by high molecular weight hyaluronate. Immunology 1980, 40:435-446.
• [13]Forrester JV, Wilkinson PC: Inhibition of leukocyte locomotion by hyaluronic acid. J Cell Sci 1981, 48:315-331.
• [14]Pisko EJ, Turner RA, Soderstrom LP, Panetti M, Foster SL, Treadway WJ: Inhibition of neutrophil phagocytosis and enzyme release by hyaluronic acid. Clin Exp Rheumatol 1983, 1:41-44.
• [15]Homandberg GA, Hui F, Wen C, Kuettner KE, Williams JM: Hyaluronic acid suppresses fibronectin fragment mediated cartilage chondrolysis. I. In vitro. Osteoarthritis Cart 1997, 5:309-319.
• [16]Williams JM, Plaza V, Hui F, Wen C, Kuettner KE, Homandberg GA: Hyaluronic acid suppresses fibronectin fragment mediated cartilage chondrolysis. II. In vivo. Osteoarthritis Cart 1997, 5:235-240.
• [17]Shimazu A, Jikko A, Iwamoto M, Koike T, Van W, Okada Y, Shinmei M, Nakamura S, Kato Y: Effects of hyaluronic acid on the release of proteoglycan from the cell matrix in rabbit chondrocyte cultures in the presence and absence of cytokines. Arthritis Rheum 1993, 36:247-253.
• [18]Gotoh S, Onaya J, Abe M, Miyazaki K, Hamai A, Horie K, Tokuyasu K: Effects of the molecular weight of hyaluronic acid and its action mechanisms on experimental joint pain in rats. Ann Rheum Dis 1993, 52:817-822.
• [19]Pozo A, Balazs EA, Belmonte C: Reduction of sensory responses to passive movements of inflamed knee joints by hylan, a hyaluronan derivative. Exp Brain Res 1997, 116:3-9.
• [20]Sunblad L: Studies on hyaluronic acid in synovial fluids. Acta Soc Med Ups 1953, 58:113-119.
• [21]Castor WC, Prince RK, Hazelton MJ: Hyaluronic acid in human synovial effusions: a sensitive indicator of altered connective tissue cell function during inflammation. Arthritis Rheum 1966, 9:783-794.
• [22]Davies DY, Palfrey AJ: Some of the physical properties of normal and pathological synovial fluid. J Biomech 1968, 1:79-88.
• [23]Balazs EA, Denlinger JL: The role of hyaluronic acid in arthritis and its therapeutic use in osteoarthritis. In In Current Clinical and Fundamental Problems. Edited by Peyron JG. Paris: Geigy; 1984:165-174.
• [24]Dahl LB, Dahl IMS, Engström-Laurent A, Granath K: Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies. Ann Rheum Dis 1985, 44:817-822.
• [25]Pitsillides AA, Worrall JG, Wilkinson LS, Bayliss MT, Edwards JCW: Hyaluronan concentration in non-inflamed and rheumatoid synovium. Br J Rheumatol 1994, 33:5-10.
• [26]Itano N, Kimata K: Hyaluronan synthase: new directions for hyaluronan research. Trends Glycosci Glycotech 1998, 10:23-28.
• [27]Recklies AD, White C, Melching L, Roughley PJ: Differential regulation and expression of hyaluronan synthases in human articular chondrocytes, synovial cells and osteosarcoma cells. Biochem J 2001, 354:17-24.
• [28]Iwanaga T, Shikichi M, Kitamura H, Yanase H, Nozawa-Inoue K: Morphology and functional roles of synoviocytes in the joint. Arch Histol Cytol 2000, 1:17-31.
• [29]Laurent UB, Fraser JR, Engstrom-Laurent A, Reed RK, Dahl LB, Laurent TC: Catabolism of hyaluronan in the knee joint of the rabbit. Matrix 1992, 12:130-136.
• [30]Csoka AB, Frost GI, Stern R: The six hyaluronidase-like genes in the human and mouse genomes [mini review]. Matrix Biol 2001, 20:499-508.
• [31]Flannery CR, Little CB, Hughes CE, Caterson B: Expression and activity of articular cartilage hyaluronidases. Biochem Biophys Res Commun 1998, 251:824-829.
• [32]Altman RD, Hochberg M, Murphy WA, Wolfe F, Lequésne M: Atlas of individual radiographic features in osteoarthritis. Osteoarthritis Cartilage 1995, Suppl A:3-70.
• [33]Miyaguchi M, Kobayashi A, Kadoya Y, Ohashi H, Yamano Y, Takaoka K: Biochemical change in joint fluid after isometric quadriceps exercise for patients with osteoarthritis of the knee. Osteoarthritis Cartilage 2003, 11:252-259.
• [34]Laurent TC, Ryan M, Pietruszkiewicz A: Fractionation of hyaluronic acid, the polydipersity of hyaluronic acid from the bovine vitreous body. Biochim Biophys Acta 1960, 42:476-485.
• [35]Heid CA, Stevens J, Williams PM: Real time quantitative PCR. Genome Res 1996, 6:986-994.
• [36]Gibson UEM, Heid CA, Williams A: Novel method for real time quantitative RT-PCR. Genome Res 1996, 6:995-1001.
• [37]Monpoeho S, Coste-Burel M, Costa-Mattioli M, Besse B, Chomel JJ, Billaudel S, Ferre V: Application of a real-time polymerase chain reaction with internal positive control for detection and quantification of enterovirus in cerebrospinal fluid. Eur J Clin Microbiol Infect Dis 2002, 21:532-536.
• [38]Cook R, Cook S, Li F, Montelaro R, Issel C: Development of a multiplex real-time reverse transcriptase-polymerase chain reaction for equine infectious anemia virus. J Virol Methods 2002, 105:171.
• [39]Yoshida M, Funasaki H, Saito M, Kajitani K, Fujii K: Pathologic gene expression in adhesive subacromial bursae of human shoulder. Clin Orthop 2003, 412:57-64.
• [40]Jacobson A, Brinck J, Briskin MJ, Spicer AP, Heldin P: Expression of human hyaluronan synthases in response to external stimuli. Biochem J 2000, 348:29-35.
• [41]Yoshida M, Itano N, Yamada Y, Kimata K: In vitro synthesis of hyaluronan by a single protein derived from mouse HAS1 gene and characterization of amino acid residues essential for the activity. J Biol Chem 2000, 275:497-506.
• [42]Itano N, Sawai T, Yoshida M, Lenas P, Yamada Y, Imagawa M, Shinomura T, Hamaguchi M, Yoshida Y, Ohnuki Y, et al.: Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem 1999, 274:25085-25092.
• [43]Nagaya H, Ymagata T, Ymagata S, Iyoda K, Ito H, Hasegawa Y, Iwata H: Examination of synovial fluid and serum hyaluronidase activity as a joint marker in rheumatoid arthritis and osteoarthritis patients (by zymography). Ann Rheum Dis 1999, 58:186-188.
• [44]Itokazu M, Shinozaki M, Ohno T: Quantitative analysis of hyaluronan in the synovial tissues of patients with joint disorders. Clin Rheumatol 1998, 17:261-262.