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

Tomochika Kisukeda,Keiji Yoshioka,Junichi Onaya

doi:10.1186/s12891-019-2586-0

Tomochika Kisukeda, Keiji Yoshioka + Show 1 more

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https://doi.org/10.1186/s12891-019-2586-0

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Journal: BMC Musculoskeletal Disorders	Publication Date: May 10, 2019
Citations: 14	License type: open-access

Affiliation: Seikagaku Corporation (Japan)

Abstract

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

Highlights

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
The culture supernatant of untreated Human fibroblast-like synoviocytes (HFLS)-rheumatoid arthritis (RA) cells provided a broad peak with a peak top at fraction no. 10 (MW = 500 kDa) in addition to the [3H] glucosamine peak (Fig. 1a)
Taken together with the result of this study and information reported by others, we suggest that the mechanism by which SI-613 induces production of High molecular weight (HMW)-hyaluronic acid (HA) larger than 2400 kDa involves the enhancement of hyaluronan synthase 2 (HAS2) Messenger RNA (mRNA) expression

Summary

Introduction

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. 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). Intra-articular (IA) injection of hyaluronic acid (hyaluronan, HA), which is a linear glycosaminoglycan composed of repeating disaccharides of glucuronic acid and N-acetylglucosamine, is a recognized treatment for pain associated with symptomatic. Kisukeda et al BMC Musculoskeletal Disorders (2019) 20:201 was anticipated that intra-articular injection of HA would be beneficial for the management of knee OA. Ikeya et al reported that exogenous HA induced the production of endogenous HA in synoviocytes from OA and RA patients [12]. The increase in endogenous HA is considered to normalize pathological synovial fluid and contributes to a long-term analgesic effect

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