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.
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