Skip to main content
SpringerLink
Log in

The synthesis of hyaluronic acid by human synovial fibroblasts is influenced by the nature of the hyaluronate in the extracellular environment

  • Originals
  • Published:
Rheumatology International Aims and scope Submit manuscript

Summary

Various cell lines of human synovial fibroblasts derived from synovium obtained at the time of biopsy or total joint-replacement surgery have been established. The synthesis of 3H-labelled hyaluronic acid (HA) in these cells has been determined, and the effects of adding HA of varying molecular size to the cultured cells examined. The results obtained clearly show that the in vitro synthesis of HA by these cells is influenced by the concentration and molecular weight (MW) of the HA in their extracellular environment. Synovial fibroblasts derived from an osteoarthritic joint demonstrated the most marked response on exposure to exogenous HA, showing a stimulation of HA synthesis with preparations of weight-average molecular weight (Mw)>5×105 in a concentration dependent manner. HA preparations with Mw<5×105 showed little or no effect except at high concentrations where a suppression of biosynthesis was observed. A model to explain these findings is proposed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Fraser JRE, Clarris BJ, Baxter E (1979) Patterns of induced variation in the morphology, hyaluronic acid secretion and lysosomal enzyme activity of cultured synovial cells. Ann Rheum Dis 38:287–294

    Google Scholar 

  2. Balazs EA, Watson D, Duff IF, Roseman S (1967) Hyaluronic acid in synovial fluid. I. Molecular parameters of hyaluronic acid in normal and arthritic human fluids. Arthritis Rheum 10:357–376

    Google Scholar 

  3. Balazs EA (1974) The physical properties of synovial fluid and the special role of hyaluronic acid. In: Helfet A (ed) Disorders of the knee. Lippincott, Philadelphia, pp 61–74

    Google Scholar 

  4. Cullis-Hill D, Ghosh P (in press) The role of hyaluronic acid in joint stability — a hypothesis for hip dysplasia and allied disorders. Med Hypotheses

  5. Castor CW, Dorstewitz EL (1966) Abnormalities of connective tissue cells cultured from patients with rheumatoid arthritis. I. Relative unresponsiveness of rheumatoid synovial cells to hydrocortisone. J Lab Clin Med 68:300–313

    Google Scholar 

  6. Vuorio E (1977) Rheumatoid disease in cultured human synovial cells — a biochemical study on glycosaminoglycans, proteins and plasma membranes of synovial fibroblasts in culture. Scand J Clin Lab Invest 37 (suppl 149):1–72

    Google Scholar 

  7. Vuorio E, Einola S, Hakkarainen S, Penttinen R (1982) Synthesis of underpolymerised hyaluronic acid by fibroblasts cultured from rheumatoid and non-rheumatoid synovitis. Rheumatol Int 2:97–102

    Google Scholar 

  8. Dahl LB, Dahl IMS, Engstrom-Laurent A, Granath K (1985) Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies. Ann Rheum Dis 44:817–822

    Google Scholar 

  9. Stephens RW, Sutherland J, Ghosh P, Taylor TKF (1976) Human serum and synovial fluid hyaluronidase — bovine testicular hyaluronidase is not a valid substitute in drug evaluation studies. Biochem Pharmacol 25:1507–1511

    Google Scholar 

  10. Kar NC, Cracchiolo A, Mirra J, Pearson CM (1976) Acid, neutral and alkaline hydrolases in arthritic synovium. Am J Clin Pathol 65:220–228

    Google Scholar 

  11. Greenwald RA, Moak SA (1986) Degradation of hyaluronic acid by polymorphonuclear leukocytes. Inflammation 10:15–30

    Google Scholar 

  12. Pigman W, Rizvi S, Holley HL (1961) Depolymerisation of hyaluronic acid by the ORD reaction. Arthritis Rheum 4:240–252

    Google Scholar 

  13. Matsumura G, Herp A, Pigman W (1966) Depolymerization of hyaluronic acid by autoxidants and radiations. Radiat Res 28:735–752

    Google Scholar 

  14. McCord JM (1974) Free radicals and inflammation: Protection of synovial fluid by superoxide dismutase. Science 185:529–531

    Google Scholar 

  15. Greenwald RA, Moy WW (1980) Effect of oxygen-derived free radicals on hyaluronic acid. Arthritis Rheum 23:455–463

    Google Scholar 

  16. McNeil JD, Wiebkin OW, Betts WH, Cleland, LG (1985) Depolymerisation products of hyaluronic acid after exposure to oxygen-derived free radicals. Ann Rheum Dis 44:780–789

    Google Scholar 

  17. Puig-Parellada P, Planas JM (1978) Synovial fluid degradation induced by free radicals. In vitro action of several free radical scavengers and anti-inflammatory drugs. Biochem Pharmacol 27:535–537

    Google Scholar 

  18. Simon RH, Scoggin CH, Patterson D (1981) Hydrogen peroxide causes the fatal injury to human fibroblasts exposed to oxygen radicals. J Biol Chem 256:7181–7186

    Google Scholar 

  19. Bates EJ, Lowther DA, Handley CJ (1984) Oxygen free-radicals mediate an inhibition of proteoglycan synthesis in cultured articular cartilage. Ann Rheum Dis 43:462–469

    Google Scholar 

  20. Bates EJ, Johnson CC, Lowther DA (1985) Inhibition of proteoglycan synthesis by hydrogen peroxide in cultured bovine articular cartilage. Biochim Biophys Acta 838:221–228

    Google Scholar 

  21. Bates EJ, Lowther DA, Johnson CC (1985) Hyaluronic acid synthesis in articular cartilage: An inhibition by hydrogen peroxide. Biochem Biophys Res Commun 132:714–720

    Google Scholar 

  22. Smith CA, Hamerman D (1969) Significance of persistent differences between normal and rheumatoid synovial membrane cells in culture. Arthritis Rheum 12:639–645

    Google Scholar 

  23. Marsh JM, Spencer S, Wiebkin O, Maini RN, Dumonde DC, Muir H (1974) Heterogeneity of human synovial tissue cultures. Ann Rheum Dis 33:578

    Google Scholar 

  24. Castor CW, Lewis RB (1976) Connective tissue activation X. Current studies of the process and its mediators. Scand J Rheumatol 5 (suppl 12):41–54

    Google Scholar 

  25. Smith CA, Hamerman D (1971) Properties of synovial cells in culture. J Exp Med 134:306–312

    Google Scholar 

  26. Castor CW, Dorstewitz EL, Rowe K, Ritchie JC (1971) Abnormalities of connective tissue cells cultured from patients with rheumatoid arthritis II. Defective regulation of hyaluronate and collagen formation. J Lab Clin Med 77:65–75

    Google Scholar 

  27. Castor CW, Smith SF, Ritchie JC, Dorstewitz EL (1971) Connective tissue activation II. Abnormalities of cultured rheumatoid synovial cells. Arthritis Rheum 14:55–66

    Google Scholar 

  28. Hamerman D, Smith C, Keiser HD, Craig R (1982) Glycosaminoglycans produced by human synovial cell cultures. Coll Rel Res 2:313–329

    Google Scholar 

  29. Dahl IMS, Husby G (1985) Hyaluronic acid production in vitro by synovial lining cells from normal and rheumatoid joints. Ann Rheum Dis 44:647–657

    Google Scholar 

  30. Barker SA, Bayyuk SHI, Brimacombe JS, Hawkins CF, Stacey M (1963) Fingerprinting the hyaluronic acid component of normal and pathological synovial fluids. Clin Chim Acta 8:902–909

    Google Scholar 

  31. Kofoed JA, Barcelo AC (1978) The synovial fluid hyaluronic acid in rheumatoid arthritis. Experentia 34:1545–1546

    Google Scholar 

  32. Balazs EA, Briller SO, Denlinger JL (1980) Na-hyaluronate molecular size variations in equine and human arthritic synovial fluids and the effect on phagocytic cells. Semin Arthritis Rheum 11 (suppl 1):141–143

    Google Scholar 

  33. Bjelle A, Andersson T, Granath K (1982) Molecular weight distribution of hyaluronic acid of human synovial fluid in rheumatic diseases. Scand J Rheumatol 12:133–138

    Google Scholar 

  34. Castor CW, Prince RK (1964) Modulation of the intrinsic viscosity of hyaluronic acid formed by human “fibroblasts” in vitro. The effects of hydrocortisone and colchicine. Biochim Biophys Acta 83:165–177

    Google Scholar 

  35. Saarni H, Tammi M, Vuorio E (1977) Effects of cortisol on glycosaminoglycans synthesized by normal and rheumatoid synovial fibroblasts in vitro. Scand J Rheumatol 6:222–224

    Google Scholar 

  36. Saarni H, Hopsu-Havu VK (1978) The decrease of hyaluronate synthesis by anti-inflammatory steroids in vitro. Br J Dermatol 98:445–449

    Google Scholar 

  37. Myers SL (1985) Suppression of hyaluronic acid synthesis in synovial organ cultures by corticosteroid suspensions. Arthritis Rheum 28:1275–1282

    Google Scholar 

  38. Kleesiek K, Greiling H (1982) Effect of anti-inflammatory agents on the glycosaminoglycan metabolism in cultured human synovial cells. Rheumatol Int 2:167–174

    Google Scholar 

  39. Verbruggen G, Veys EM (1977) Influence of sulphated glycosaminoglycans upon proteoglycan metabolism of the synovial lining cells. Acta Rheumatol 1:75–92

    Google Scholar 

  40. Smith MM, Ghosh P (1986) The effects of some polysulphated polysaccharides on hyaluronate (HA) synthesis by human synovial fibroblasts. Agents and Actions [Suppl] 18:55–62

    Google Scholar 

  41. Hamerman D, Wood DD (1984) Interleukin I enhances synovial cell hyaluronate synthesis. Proc Soc Exp Biol Med 177:205–210

    Google Scholar 

  42. Heino J (1986) Connective tissue components in synovial fibroblast cultures exposed to interleukin I and prostaglandin E2. Virchows Arch [Cell Pathol] 50:313–320

    Google Scholar 

  43. Peyron JG, Balazs EA (1974) Preliminary clinical assessment of Na-hyaluronate injection into human arthritic joints. Pathol Biol 22:731–736

    Google Scholar 

  44. Weiss C, Balazs EA, St Onge R, Denlinger JL (1980) Clinical studies of the intraarticular injection of Healon (sodium hyaluronate) in the treatment of osteoarthritis of human knees. Semin Arthritis Rheum 11 (suppl 1):143–144

    Google Scholar 

  45. Namiki O, Toyoshima H, Morisaki N (1982) Therapeutic effect of intra-articular injection of high molecular weight hyaluronic acid on osteoarthritis of the knee. Int J Clin Pharmacol Ther Toxicol 20:501–507

    Google Scholar 

  46. Kopp S, Wenneberg B, Haraldson T, Carlsson GE (1985) The short-term effect of intra-articular injections of sodium hyaluronate and corticosteroid on temporomandibular joint pain and dysfunction. J Oral Maxillofac Surg 43:429–435

    Google Scholar 

  47. Rydell NW, Butler J, Balazs EA (1970) Hyaluronic acid in synovial fluid. VI. Effect of intra-articular injection of hyaluronic acid on the clinical symptoms of arthritis in track horses. Acta Vet Scand 11:139–155

    Google Scholar 

  48. Rydell N, Balazs EA (1971) Effect of intra-articular injection of hyaluronic acid on the clinical symptoms of osteoarthritis and on granulation tissue formation. Clin Orthop 80:25–32

    Google Scholar 

  49. Asheim A, Lindblad G (1976) Intra-articular treatment of arthritis in race-horses with sodium hyaluronate. Acta Vet Scand 17:379–394

    Google Scholar 

  50. Auer TA, Fackelman GE, Gingerich DA, Fetter AW (1980) Effect of hyaluronic acid in naturally occurring and experimentally induced osteoarthritis. Am J Vet Res 41:568–574

    Google Scholar 

  51. Phillips MW (1980) Intra-articular sodium hyaluronate in the horse: A clinical trial. Proc 26th Ann Conv AAEP, pp 389–394

  52. Gingerich DA, Auer JA, Fackelman GE (1981) Effect of exogenous hyaluronic acid on joint function in experimentally induced equine osteoarthritis: dosage titration studies. Res Vet Sci 30:192–197

    Google Scholar 

  53. Dayer J-M, Krane SM, Russell RGG, Robinson DR (1976) Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells. Proc Natl Acad Sci USA 73:945–949

    Google Scholar 

  54. Burton K (1968) Determination of DNA concentration with diphenylamine. In: Colowick SP, Kaplan NO (eds) Methods in enzymology, part 12/1B. Academic Press, New York London, pp 163–166

    Google Scholar 

  55. Blumenkrantz N, Asboe-Hansen G (1973) New method for quantitative determination of uronic acids. Anal Biochem 54:484–489

    Google Scholar 

  56. Peterson GL (1977) A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem 83:346–356

    Google Scholar 

  57. Ohya T, Kaneko Y (1970) Novel hyaluronidase from streptomyces. Biochim Biophys Acta 98:607–609

    Google Scholar 

  58. Balazs EA, Darzynkiewicz Z (1973) The effect of hyaluronic acid on fibroblasts, mononuclear phagocytes and lymphocytes, In: Kulonen E, Pikkarainen J (eds) Biology of fibroblast. Academic Press, New York London, pp 237–252

    Google Scholar 

  59. Wiebkin OW, Muir H (1973) The inhibition of sulphate incorporation in isolated adult chondrocytes by hyaluronic acid. FEBS Lett 37:42–46

    Google Scholar 

  60. Wiebkin OW, Hardingham TE, Muir H (1975) Hyaluronic acid-proteoglycan interaction and the influence of hyaluronic acid on proteoglycan synthesis by chondrocytes from adult cartilage. In: Slavkin HC, Greulich RC (eds) Extracellular matrix influences on gene expression. Academic Press, New York London, pp 209–223

    Google Scholar 

  61. Wiebkin OW, Muir H (1975) Influence of the cells of the pericellular environment. The effect of hyaluronic acid on proteoglycan synthesis and secretion by chondrocytes of adult cartilage. Philos Trans R Soc Lond 271:283–291

    Google Scholar 

  62. Wiebkin OW, Muir H (1977) Synthesis of proteoglycans by suspension and monolayer cultures of adult chondrocytes and de novo cartilage nodules — the effect of hyaluronic acid. J Cell Sci 27:199–211

    Google Scholar 

  63. Toole BP (1973) Hyaluronate and hyaluronidase in morphogenesis and differentiation. Am Zool 13:1061–1065

    Google Scholar 

  64. Solursh M, Vaerewyck SA, Reiter RS (1974) Depression by hyaluronic acid of glycosaminoglycan synthesis by cultured chick embryo chondrocytes. Dev Biol 41:233–244

    Google Scholar 

  65. Handley CJ, Lowther DA (1978) Inhibition of proteoglycan biosynthesis by hyaluronic acid in chondrocytes in cell culture. Biochim Biophys Acta 444:69–74

    Google Scholar 

  66. Meier S, Hay ED (1974) Stimulation of extracellular matrix synthesis in the developing cornea by glycosaminoglycans. Proc Natl Acad Sci USA 71:2310–2313

    Google Scholar 

  67. Angello JC, Hauschka SD (1980) Hyaluronate-cell interaction. Effects of exogenous hyaluronate on muscle fibroblast cell surface composition. Exp Cell Res 125:389–400

    Google Scholar 

  68. Wigren A, Wik O (1974) The influence of hyaluronic acid on immobilized knees. An experimental study on adult rabbits. Ups J Med Sci [Suppl] 16:1–26

    Google Scholar 

  69. Weiner LB (1985) Applications of sodium hyaluronate in equine practice. Equine Vet Sci 5:210–216

    Google Scholar 

  70. Prehm P (1984) Hyaluronate is synthesized at plasma membranes. Biochem J 220:597–600

    Google Scholar 

  71. Underhill CB, Toole BP (1979) Binding of hyaluronate to the surface of cultured cells. J Cell Biol 82:475–484

    Google Scholar 

  72. Underhill CB, Toole BP (1980) Physical characteristics of hyaluronate binding to the surface of Simian Virus 40-transformed 3T3 cells. J Biol Chem 255:4544–4549

    Google Scholar 

  73. Underhill CB, Toole BP (1981) Receptors for hyaluronate on the surface of parent and virus-transformed cell lines. Binding and aggregation studies. Exp Cell Res 131:419–423

    Google Scholar 

  74. Laurent TC, Fraser JRE, Pertoft H, Smedsrod B (1986) Binding of hyaluronate and chondroitin sulfate to liver endothelial cells. Biochem J 234:653–658

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Raymond Purves Research Laboratories, University of Sydney, Royal North Shore Hospital, 2065, St. Leonards, N.S.W., Australia

    M. M. Smith & P. Ghosh

Authors
  1. M. M. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, M.M., Ghosh, P. The synthesis of hyaluronic acid by human synovial fibroblasts is influenced by the nature of the hyaluronate in the extracellular environment. Rheumatol Int 7, 113–122 (1987). https://doi.org/10.1007/BF00270463

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00270463

Key words

Search

Navigation