Skip to main content
Top
Published in: BMC Musculoskeletal Disorders 1/2019

Open Access 01-12-2019 | Osteoarthrosis | Research article

Effect of diclofenac etalhyaluronate (SI-613) on the production of high molecular weight sodium hyaluronate in human synoviocytes

Authors: Tomochika Kisukeda, Junichi Onaya, Keiji Yoshioka

Published in: BMC Musculoskeletal Disorders | Issue 1/2019

Login to get access

Abstract

Background

We have reported that a single intra-articular injection of diclofenac etalhyaluronate (SI-613) exerted a potent and long-lasting analgesic effect in experimental arthritis models. In the present study, we investigated the effect of SI-613 on the production of high molecular weight hyaluronic acid (HMW-HA) in synoviocytes from osteoarthritis (OA) patients and compared its efficacy with that of hyaluronic acid (HA).

Methods

We compared the effect of SI-613, HA, and diclofenac sodium (DF-Na) on high molecular weight HA production by human synoviocytes.

Results

SI-613 and exogenous HA induced the production of high molecular weight HA in synoviocytes from OA patients, whereas DF-Na had no effect. The molecular weight of newly produced HA was about 1000 kDa in the HA-treated synoviocytes and much higher than 2400 kDa in the SI-613-treated cells. The effect of the mixture of HA and DF-Na was similar to that of HA alone in that the molecular weight of newly produced HA was around 1000 kDa. SI-613 significantly suppressed hyaluronidase 2 (HYAL2) mRNA expression and significantly enhanced hyaluronan synthase 2 (HAS2) mRNA expression. HA had no effect on the expression levels of HYAL and HAS.

Conclusion

The present results clearly demonstrate that SI-613 induces the production of high molecular weight HA in synoviocytes from OA patients, suggesting the long-lasting analgesic and disease modifying effect of SI-613 for OA. Taken together with the anti-inflammatory and analgesic effects we recently reported for the intra-articular administration of SI-613 to experimental animal models, SI-613 holds great promise for the treatment of knee osteoarthritis.
Literature
1.
go back to reference Buckwalter JA, Saltzman C, Brown T. The impact of osteoarthritis: implications for research. Clin Orthop Relat Res. 2004;427(Suppl):S6–15.CrossRef Buckwalter JA, Saltzman C, Brown T. The impact of osteoarthritis: implications for research. Clin Orthop Relat Res. 2004;427(Suppl):S6–15.CrossRef
2.
go back to reference Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartil. 2008;16:137–62.CrossRef Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthr Cartil. 2008;16:137–62.CrossRef
3.
go back to reference Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, et al. OARSI recommendations for the management of hip and knee osteoarthritis part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil. 2010;18:476–99.CrossRef Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, et al. OARSI recommendations for the management of hip and knee osteoarthritis part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthr Cartil. 2010;18:476–99.CrossRef
4.
go back to reference Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000;43:1905–15.CrossRef Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000;43:1905–15.CrossRef
5.
go back to reference Balazs EA, Bloom GD, Swann DA. Fine structure and glycosaminoglycan content of the surface layer of articular cartilage. Fed Proc. 1966;25:1813–6.PubMed Balazs EA, Bloom GD, Swann DA. Fine structure and glycosaminoglycan content of the surface layer of articular cartilage. Fed Proc. 1966;25:1813–6.PubMed
6.
go back to reference Balazs EA. The physical properties of synovial fluid and the special role of hyaluronic acid. In disorders of the knee. (ed. by AJ Helfet) Lippincott Co., Philadelphia, 1974, 63–75. Balazs EA. The physical properties of synovial fluid and the special role of hyaluronic acid. In disorders of the knee. (ed. by AJ Helfet) Lippincott Co., Philadelphia, 1974, 63–75.
7.
go back to reference Dahl LB, Dahl IM, 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(12):817–22.CrossRef Dahl LB, Dahl IM, 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(12):817–22.CrossRef
8.
go back to reference Ogston AG, Stanier JE. The physiological function of hyaluronic acid in synovial fluid; viscous, elastic and lubricant properties. J Physiol. 1953;119(2–3):244–52.CrossRef Ogston AG, Stanier JE. The physiological function of hyaluronic acid in synovial fluid; viscous, elastic and lubricant properties. J Physiol. 1953;119(2–3):244–52.CrossRef
9.
go back to reference Altman RD, Dasa V, Takeuchi J. Review of the mechanism of action for Supartz FX in knee osteoarthritis. Cartilage. 2018;9(1):11–20.CrossRef Altman RD, Dasa V, Takeuchi J. Review of the mechanism of action for Supartz FX in knee osteoarthritis. Cartilage. 2018;9(1):11–20.CrossRef
10.
go back to reference Santangelo KS, Johnson AL, Ruppert AS, Bertone AL. Effects of hyaluronan treatment on lipopolysaccharide-challenged fibroblast-like synovial cells. Arthritis Res Ther. 2007;9:R1.CrossRef Santangelo KS, Johnson AL, Ruppert AS, Bertone AL. Effects of hyaluronan treatment on lipopolysaccharide-challenged fibroblast-like synovial cells. Arthritis Res Ther. 2007;9:R1.CrossRef
11.
go back to reference Asari A, Miyauchi S, Matsuzaka S, Ito T, Kominami E, Uchiyama Y. Molecular weight-dependent effects of hyaluronate on the arthritic synovium. Arch Histol Cytol. 1998;61(2):125–35.CrossRef Asari A, Miyauchi S, Matsuzaka S, Ito T, Kominami E, Uchiyama Y. Molecular weight-dependent effects of hyaluronate on the arthritic synovium. Arch Histol Cytol. 1998;61(2):125–35.CrossRef
12.
go back to reference Ikeya H, Miyoshi T, Nakamura T, Endo M. Hyaluronate degradation and synthesis by cultured synovial fibroblasts derived from knee joints of patients suffering from rheumatoid arthritis and osteoarthritis. Connective Tissue. 1994;25:243–9. Ikeya H, Miyoshi T, Nakamura T, Endo M. Hyaluronate degradation and synthesis by cultured synovial fibroblasts derived from knee joints of patients suffering from rheumatoid arthritis and osteoarthritis. Connective Tissue. 1994;25:243–9.
13.
go back to reference Yoshioka K, Kisukeda T, Zuinen R, Yasuda Y, Miyamoto K. Pharmacological effects of N-[2-[[2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetyl]oxy]ethyl] hyaluronamide (diclofenac etalhyaluronate, SI-613), a novel sodium hyaluronate derivative chemically linked with diclofenac. BMC Musculoskelet Disord. 2018;19:157.CrossRef Yoshioka K, Kisukeda T, Zuinen R, Yasuda Y, Miyamoto K. Pharmacological effects of N-[2-[[2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetyl]oxy]ethyl] hyaluronamide (diclofenac etalhyaluronate, SI-613), a novel sodium hyaluronate derivative chemically linked with diclofenac. BMC Musculoskelet Disord. 2018;19:157.CrossRef
14.
go back to reference David-Raoudi M, Deschrevel B, Leclercq S, Galéra P, Boumediene K, Pujol JP. Chondroitin sulfate increases hyaluronan production by human synoviocytes through differential regulation of hyaluronan synthases: role of p38 and Akt. Arthritis Rheum. 2009;60:760–70.CrossRef David-Raoudi M, Deschrevel B, Leclercq S, Galéra P, Boumediene K, Pujol JP. Chondroitin sulfate increases hyaluronan production by human synoviocytes through differential regulation of hyaluronan synthases: role of p38 and Akt. Arthritis Rheum. 2009;60:760–70.CrossRef
15.
go back to reference Balazs EA, Watson D, Duff IF, Roseman S. Hyaluronic acid in synovial fluid. I. Molecular parameters of hyaluronic acid in normal and arthritis human fluids. Arthritis Rheum. 1967;10:357–76.CrossRef Balazs EA, Watson D, Duff IF, Roseman S. Hyaluronic acid in synovial fluid. I. Molecular parameters of hyaluronic acid in normal and arthritis human fluids. Arthritis Rheum. 1967;10:357–76.CrossRef
16.
go back to reference Itano N, Kimata K. Mammalian hyaluronan synthases. IUBMB Life. 2002;54:195–9.CrossRef Itano N, Kimata K. Mammalian hyaluronan synthases. IUBMB Life. 2002;54:195–9.CrossRef
17.
go back to reference Brinck J, Heldin P. Expression of recombinant hyaluronan synthase (HAS) isoforms in CHO cells reduces cell migration and cell surface CD44. Exp Cell Res. 1999;252:342–51.CrossRef Brinck J, Heldin P. Expression of recombinant hyaluronan synthase (HAS) isoforms in CHO cells reduces cell migration and cell surface CD44. Exp Cell Res. 1999;252:342–51.CrossRef
18.
go back to reference Stern R. Hyaluronan metabolism: a major paradox in cancer biology. Pathol Biol. 2005;53:372–82.CrossRef Stern R. Hyaluronan metabolism: a major paradox in cancer biology. Pathol Biol. 2005;53:372–82.CrossRef
19.
go back to reference Smith MM, 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. 1987;7:113–22.CrossRef Smith MM, 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. 1987;7:113–22.CrossRef
Metadata
Title
Effect of diclofenac etalhyaluronate (SI-613) on the production of high molecular weight sodium hyaluronate in human synoviocytes
Authors
Tomochika Kisukeda
Junichi Onaya
Keiji Yoshioka
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2019
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-019-2586-0

Other articles of this Issue 1/2019

BMC Musculoskeletal Disorders 1/2019 Go to the issue