Abstract

Evidence indicates that hyaluronic acid (HA) mitigates tendinopathy, but the effect of molecular weight is unclear. We investigated the effects of different concentrations and different molecular weights of HA (350 kDa, 1500 kDa, and 3000 kDa) on matrix metalloproteinase (MMP)-1 and -3 expression in IL-1β-stimulated rat tenocytes, and on their dynamic expression in peritendinous effusion from patients with long head of biceps (LHB) tendinopathy after high-molecular-weight (HMW)-HA treatments. Reverse transcription PCR, real-time PCR, and ELISA were used to determine MMP-1 and -3expression. Because CD44 was clearly expressed in the plasma membranes of cultured tenocytes, OX-50, a CD44 antagonist, was used to inhibit CD44 to evaluate the HA mechanism. HA (3000 kDa) significantly (p < 0.001) downregulated the mRNA and protein expression of MMP-1 and -3 in IL-1β-stimulated tenocytes. Its attenuating effects were dose-dependent (p < 0.01). In OX-50-pretreated cells, the mRNA expression of CD44 was not significantly altered, but the mRNA expression of MMP-1 and -3 was significantly upregulated. Visual analogue scale scores were significantly lower, and MMP-1 and -3 expression was significantly (p < 0.05) lower one month posttreatment. HMW-HA attenuated tendinopathy by downregulating MMP-1 and -3 expression. Inhibiting CD44 blocked the effects of HMW-HA.

Highlights

  • We investigated the effects of three molecular weights and three concentrations of hyaluronic acid (HA) on the expression of MMP-1 and -3 in IL-1β-stimulated tenocytes from rat Achilles tendons

  • Every cell was immunopositive for tenomodulin, the tenocyte marker (Fig. 1), which confirmed that the primary cultured cells were tenocytes

  • Effects of HA on tenocyte proliferation and viability. After they had been treated with IL-1β,or with HA of various molecular weights, or with both for 24 h, there were no obvious morphologically changed tenocytes that maintained a bipolar and spindle shape

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Summary

Introduction

Others[21,23] have reported significantly elevated MMP-1 and -3 expression after IL-1βstimulation in human tendon cells and have made IL-1βa candidate for an in vitro tendinopathy model. We hypothesized that HMW-HA downregulates MMP-1 and -3 expression by stimulating CD44 receptor in tendinopathy. We investigated the effects of three molecular weights and three concentrations of HA on the expression of MMP-1 and -3 in IL-1β-stimulated tenocytes from rat Achilles tendons. Bicipital peritendinous effusion has been reported strong association with LHB tendinopathy[28] and is the result of the excess synovial secretion by the tendon sheath[30]. We evaluated the dynamic MMP-1 and -3 expression in peritendinous effusion from patients with LHB tendinopathy after HMW-HA treatments. Tenocytes were pretreated with OX-50 (anti-CD44 antibody) to evaluate the mechanism of action of HA

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