1. Ultrasound-targeted microbubble destruction facilitates cartilage repair through increased the migration of mesenchymal stem cells via HIF-1α-mediated glycolysis pathway in rats.
- Author
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Kong F, Xia P, Shi Y, Ye Z, Zhang X, Yu C, Cheng K, and Li X
- Subjects
- Animals, Rats, Mesenchymal Stem Cell Transplantation methods, Male, Ultrasonic Waves, Cartilage, Articular metabolism, Cartilage, Articular pathology, Chondrocytes metabolism, Cells, Cultured, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells cytology, Glycolysis, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Cell Movement, Microbubbles, Rats, Sprague-Dawley, Osteoarthritis metabolism, Osteoarthritis therapy, Osteoarthritis pathology
- Abstract
Objective: Mesenchymal stem cells (MSCs) can treat osteoarthritis (OA), but their therapeutic efficacy is poor to date due to low migration efficiency. This study aimed to determine whether ultrasound-targeted microbubble destruction (UTMD) could ameliorate cartilage repair efficiency through facilitating the migration of MSCs via hypoxia-inducible factor-1α (HIF-1α)-mediated glycolysis regulatory pathway in OA model rats., Methods: OA rats were treated with MSCs alone or in combination with UTMD, respectively, for 4 weeks. Cartilage histopathology, MSCs migration efficiency, von Frey fiber thresholds, and the expression levels of collagen II and MMP-13 were measured. Further, MSCs were extracted from the bone marrow of rats, cocultured with osteoarthritic chondrocytes, transfected to siRNA-HIF-1α, and subjected to UTMD for 4 days. Glucose consumption, lactate production, and cell migration efficiency were assessed. The protein expression levels of HIF-1α, HK2, PKM2, and GLUT1 were measured, respectively., Results: In OA rat model, NC-MSCs + UTMD improved migration efficiency, increased collagen II expression, decreased MMP-13 expression, and delayed osteoarthritis progression. Silencing HIF-1α attenuated the effects induced by UTMD. In vitro, UTMD led to increases in MSC activity and migration, glucose consumption, lactate production, and the protein expression of HIF-1α, HK2, PKM2, and GLUT1 expression, all of which were reversed upon HIF-1α silencing., Conclusion: UTMD enhances MSCs migration and improves cartilage repair efficiency through the HIF-1α-mediated glycolytic regulatory pathway, providing a novel therapy strategy for knee osteoarthritis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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