Lithium-Containing Biomaterials Stimulate Cartilage Repair Through Bone Marrow Stromal Cell-Derived Exosomal miR-455-3p and Histone H3 Acetylation.

The repair of damaged cartilage still remains a great challenge in clinic. It is demonstrated that bone marrow stromal cells (BMSCs)-chondrocytes communication is of great significance for cartilage repair. Moreover, BMSCs have been confirmed to enhance biological function of chondrocytes via exosome-mediated paracrine pathway. Lithium-containing scaffolds have been reported to effectively promote cartilage regeneration; however, whether Lithium-containing biomaterial could facilitate cartilage regeneration through regulating BMSCs-derived exosomes has not been illustrated. In our study, the model Lithium-substituted bioglass ceramic (Li-BGC) is selected and regulatory effects of BMSCs-derived exosomes after Li-BGC treatment (Li-BGC-Exo) are systemically evaluated. The data reveal that Li-BGC-Exo notably promotes chondrogenesis, which attributes to the upregulated exosomal miR-455-3p transfer, consequently leads to suppression of HDAC2 and enhanced histone H3 acetylation in chondrocytes. Notably, LiCl-Exo exhibits the similar regulatory effect with Li-BGC-Exo, indicating that the pro-chondrogenesis capability of them is mainly owing to the Lithium ions. Furthermore, the in vivo study prove that LiCl-Exo remarkably facilitates cartilage regeneration. Our research may provide novel possibility for the intrinsic mechanism of chondrogenesis trigged by Lithium-containing biomaterials, and suggest that application of Lithium-containing scaffolds may be a promising strategy for cartilage regeneration. This article is protected by copyright. All rights reserved.