Icariin is a class IV drug of low solubility, permeability, and poor bioavailability. Synthetic nanomaterials have developed rapidly. However, some literatures point out that synthetic nanomaterials such as liposomes, aptamers, metal nanoparticles, and nanogels have high toxicity and are affected by the reticuloendothelial system or mononuclear phagocyte system. It is known that exosomes could be used as an ideal clinical drug delivery vehicle to avoid the above-mentioned problems to a certain extent. Studies have shown that drugs can be loaded into exosomes by passive and active loading. We used Fetal bovine serum (FBS) exosomes to carry Icariin for the first time in this experiment, FBS exosomes-Icariin (FBS EXO-ICA) more effectively promoted the proliferation of osteoblasts and bone regeneration than Icariin alone. FBS EXO-ICA could become a new nano scale drug formulation for treating diseases associated with bone loss.
Small extracellular vesicles (sEVs) are an important component in the paracrine pathway. They can be used as a substitute for seed cells and have shown good application prospects in promoting bone regeneration. Cow’s milk could be used as a source of sEVs with good biocompatibility and cost-effectiveness, with easy availability, low cost and low toxicity. This study focused on the role and mechanism of small extracellular vesicles derived from milk in bone repair. In order to explore the mechanism via which Milk-sEVs promote bone repair, we screened the differential gene GJA1 in Milk-sEV-treated osteoblasts through transcriptome chips, and verified the transcript AP3B1 of GJA1 through chromatin immunoprecipitation (CHIP). We have proved by in vivo and in vitro experiments that milk-derived sEVs (Milk-sEVs) increase the repair ability of bone tissue, and promote expression of the osteogenic gene GJA1 through the transcript AP3B1. Graphical abstract
BackgroundSmall extracellular vesicles (sEVs) are an important component in the paracrine pathway. They can be used as a substitute for seed cells and have shown good application prospects in promoting bone regeneration. Cow’s milk could be used as a source of sEVs with good biocompatibility and cost-effectiveness, with easy availability, low cost and low toxicity. This study focused on the role and mechanism of small extracellular vesicles derived from milk in bone repair.MethodssEVs were isolated from fresh milk by ultracentrifugation, and the extraction of Milk-sEVs was identified by TEM, NTA, and Western blotting. The effects of Milk-sEVs on the proliferation and differentiation of osteoblasts were studied by CCK-8 assay, ALP, Western blotting and Real-time PCR. A mice skull defect model was constructed, and the bone formation at the defect site was observed by HE staining, Masson staining and IHC. The differential gene GJA1 after Milk-sEVs acted on osteoblasts was screened by transcriptome chip, and the transcript AP3B1 of GJA1 was verified by CHIP.ResultsWe have proved by in vivo and in vitro experiments that milk-derived sEVs (Milk-sEVs) increase the repair ability of bone tissue, and promote expression of the osteogenic gene GJA1 through the transcript AP3B1.ConclusionMilk-sEVs can enhance the expression of the transcription factor AP3B1, AP3B1 can bind to the GJA1 promoter to enhance the expression of GJA1 and promote bone repair.
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