Radial extracorporeal shockwave promotes subchondral bone stem/progenitor cell self-renewal by activating YAP/TAZ and facilitates cartilage repair in vivo

作者：Zhidong Zhao, Yuxing Wang, Qian Wang, Jia-Wu Liang, Wei Hu, Sen Zhao, Peilin Li, Heng Zhu, Zhongli Li · 发表于：Stem Cell Research & Therapy · 年份：2021 · DOI：10.1186/s13287-020-02076-w · 被引用次数：28 · 研究领域：Tendon Structure and Treatment、Hippo pathway signaling and YAP/TAZ、Periodontal Regeneration and Treatments

BACKGROUND: Radial extracorporeal shockwave (r-ESW), an innovative and noninvasive technique, is gaining increasing attention in regenerative medicine due to its mechanobiological effects. Subchondral bone stem/progenitor cells (SCB-SPCs), originating from the pivotal zone of the osteochondral unit, have been shown to have multipotency and self-renewal properties. However, thus far, little information is available regarding the influences of r-ESW on the biological properties of SCB-SPCs and their therapeutic effects in tissue regeneration. METHODS: SCB-SPCs were isolated from human knee plateau osteochondral specimens and treated with gradient doses of r-ESW in a suspension stimulation system. The optimized parameters for SCB-SPC self-renewal were screened out by colony-forming unit fibroblast assay (CFU-F). Then, the effects of r-ESW on the proliferation, apoptosis, and multipotency of SCB-SPCs were evaluated. Moreover, the repair efficiency of radial shockwave-preconditioned SCB-SPCs was evaluated in vivo via an osteochondral defect model. Potential mechanisms were explored by western blotting, confocal laser scanning, and high-throughput sequencing. RESULTS: The CFU-F data indicate that r-ESW could augment the self-renewal of SCB-SPCs in a dose-dependent manner. The CCK-8 and flow cytometry results showed that the optimized shockwave markedly promoted SCB-SPC proliferation but had no significant influence on cell apoptosis. Radial shockwave exerted no significant influenc...