Objective: Dysregulation of the anabolic processes in a proinflammatory joint environment coupled with impeded chondrogenic differentiation of mesenchymal stromal cells (MSCs) led to inferior cartilage repair outcomes. The preponderance of proinflammatory cytokines activated nuclear factor kappa B (NFκB) and impeded the chondrogenesis of MSCs. Thus, strategies that minimize the deleterious effects of activated NFκB while promoting MSC chondrogenesis are of interest. The present study establishes the ability of continuous low-intensity ultrasound (cLIUS) to rescue MSC chondrogenesis impacted by a proinflammatory environment. Methods: Human bone marrow-derived MSCs were seeded in alginate:collagen hydrogels and cultured for 21-days in an ultrasound-assisted bioreactor 14 kPa (5.0 MHz, 2.5 Vpp; 4-applications/day) for 21 days in the presence of IL1β and evaluated by qRT-PCR (n=10), immunofluorescence (n=15), western blotting (WB) (n=6), and immunohistochemistry (n=3). The differential expression of markers associated with NFκB pathway under cLIUS were evaluated upon a single exposure of cLIUS and assayed by qRT-PCR (n=3), immunofluorescence (n=30-60), WB (n=6) and tetramethylrhodamine methyl ester assay (n=50) was used to assess the mitochondrial potential under IL1β and cLIUS treatment.Results: Chondroinductive potential of cLIUS was preserved as noted by the increased expression of SOX9 and deposition of collagen II. cLIUS extended its chondroprotective effects by stabilizing the NFκB complex in the cytoplasm via engaging the IκBα feedback mechanism, thus preventing its nuclear translocation. cLIUS acted as a mitochondrial protective agent by restoring the mitochondrial potential and the mitochondrial mRNA expression in a proinflammatory environment. Conclusion: Our results demonstrated the potential of cLIUS for cartilage repair and regeneration under proinflammatory conditions.
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