Glyburide Accelerates the Process of Tendon Healing by Inhibiting NLRP3 Inflammasome in Calcific Tendinopathy.

Abstract

BACKGROUND The NOD-like receptor protein 3 (NLRP3) inflammasome activated by calcific crystals is particularly relevant to the initiation and progression of calcific tendinopathy. Moreover, NLRP3 inflammasome-driven inflammation controlled at low-grade levels could promote collagen regeneration of the tendon. Recently, it has been reported that glyburide, a hypoglycemic drug, inhibits the NLRP3 inflammasome, a possible diagnostic biomarker and therapeutic target for calcific tendinopathy. STUDY DESIGN Controlled laboratory study. PURPOSE To investigate whether glyburide has therapeutic effects on calcific tendinopathy and to determine the role of the NLRP3 inflammasome in such an effect. METHODS A total of 60 Sprague-Dawley rats underwent collagenase injection into the Achilles tendon to induce calcific tendinopathy. Sixteen weeks later, the rats were randomly assigned to 3 groups: (1) 10% dimethyl sulfoxide (DMSO) group, (2) celecoxib group, and (3) glyburide group. Gross morphological and histological analyses were conducted to evaluate tendon healing. Additionally, real-time quantitative polymerase chain reaction and Western blotting were performed to assess whether glyburide degeneration influences the expression of components of the NLRP3 inflammasome, including NLRP3, apoptosis-associated speckle-like protein (ASC), caspase-1, IL-1β, and IL-18, within Achilles tendon enthesis at 2 weeks after treatment. RESULTS The Achilles tendon tissues in the glyburide group exhibited significantly less degeneration and fewer calcium deposits compared with the celecoxib and DMSO groups. The mRNA and protein expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 were reduced in the glyburide group compared with both the celecoxib and DMSO groups. CONCLUSION Glyburide targets the upstream NLRP3 signaling pathway, potentially accelerating tendon healing, which may contribute to advancements in the treatment of calcific tendinopathy. CLINICAL RELEVANCE Glyburide acts as an NLRP3 inflammasome inhibitor and may be a new option for tendon healing in calcific tendinopathy.