Viscosupplementation: Evidence for a Mechanism of Action

Authors: DD Waddell et al.

References: Presented at AAOS 2004

Hyaluronan in this study reduced MMP activity induced by IL-1 of synovial cells in osteoarthritis patients.

INTRODUCTION: Viscosupplementation is approved for treating pain due to osteoarthritis (OA). One possible mechanism is the reduction in expression of cartilage-destroying enzymes (metalloproteinases (MMPs)), which are produced in response to proinflammatory cytokines such as IL-1. We hypothesized that hyaluronan (HA), the substance used in viscosupplementation, reduced MMP activity of synovial cells in OA patients induced by IL-1.

METHODS: Surgical biopsies (0.12 square cm, +/-15 percent) were obtained from 20 patients undergoing total-knee replacement for OA. The biopsies were cultured for 24 hrs in serumless medium in the presence or absence of IL-1 (100 pg/ml) and HA (8 mg/ml), and the MMP activity of the supernatant (principally collagenase) was measured using a film of collagen as the substrate. The three HA products approved by FDA for viscosupplementation and one additional HA were studied. The HA’s and their respective molecular weights were: Synvisc (6 MDa); Supartz (0.6-1.1 MDa); Hyalgan (0.5 MDa); 0.2 MDa HA (Lifecore). The effect of HA on the IL-1-induced MMP production was evaluated using the unpaired t-test; enzyme activities are expressed in units of mg of substrate digested per hour per square meter.

RESULTS: The synovial biopsies produced a constitutive MMP activity of 2.7+/-1.2, which was increased 16-fold (to 44.7+/-4.8) in response to treatment with IL-1. When 0.2 MDa HA was added together with the cytokine, the MMP activity was unaffected (45.0+/-5.5). The MMP activities measured in the presence of IL-1 and viscosupplementation HA’s were: 27.9+/-5.7, Hyalgan; 7.8+/-4.3, Supartz; 3.6+/-1.1, Synvisc (P<0.05 compared with IL-1 alone for all 3 HA’s). Fat biopsies produced only a negligible amount of MMP activity, indicating that the enzymatic activity in the synovial biopsies was produced by synovial cells.

CONCLUSION: Viscosupplementation HA’s blocked the IL-1-induced MMP activity produced by synovial cells in a process that depended on HA molecular weight; maximum inhibition occurred at the highest molecular weight (6.1 MDa). It is not possible to reach conclusions regarding the relative abilities of the HA’s to inhibit cytokine-induced MMP activity when the HA’s are used at the FDA-approved concentrations (10 mg/ml, except 8 mg/ml for Synvisc). Even so, the results established that the viscosupplementation HA’s can inhibit cytokine-induced MMP activity, as hypothesized, suggesting that the mode of action of HA might be due to reduced MMP activity with concomitant reduction in inflammatory-mediated pain.


Find a Shoulder Professional

+ Add Your Clinic Advanced Search

This website is certified by Health On the Net Foundation. Click to verify. This site complies with the HONcode standard for trustworthy health information:
verify here. satisfies the INTUTE criteria for quality and has been awarded 'editor's choice'.

The material on this website is designed to support, not replace, the relationship that exists between ourselves and our patients. Full Disclaimer