Lithium‐Containing Biomaterials Stimulate Cartilage Repair through Bone Marrow Stromal Cells‐Derived Exosomal miR‐455‐3p and Histone H3 Acetylation

Abstract

AbstractThe 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 the 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 histone deacetylase 2 (HDAC2) and enhanced histone H3 acetylation in chondrocytes. Notably, BMSCs‐derived exosomes after LiCl treatment (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 proves that LiCl‐Exo remarkably facilitates cartilage regeneration. The research may provide novel possibility for the intrinsic mechanism of chondrogenesis trigged by lithium‐containing biomaterials, and suggests that application of lithium‐containing scaffolds may be a promising strategy for cartilage regeneration.