Search

Osteoporosis (OP) is a systematic bone disease characterized by low bone mass and fragile bone microarchitecture. Conventional treatment for OP has limited efficacy and long-term toxicity. Synthetic biology makes bacterial extracellular vesicle (BEVs)-based therapeutic strategies a promising alternative for the treatment of OP. Here, we constructed a recombinant probiotics Escherichia coli Nissle 1917-pET28a-ClyA-BMP-2-CXCR4 (ECN-pClyA-BMP-2-CXCR4), in which BMP-2 and CXCR4 were overexpressed in fusion with BEVs surface protein ClyA. Subsequently, we isolated engineered BEVs-BMP-2-CXCR4 (BEVs-BC) for OP therapy. The engineered BEVs-BC exhibited great bone targeting in vivo. In addition, BEVs-BC had good biocompatibility and remarkable ability to promote osteogenic differentiation of BMSCs. Finally, the synthetic biology-based BEVs-BC significantly prevented the OP in an ovariectomized (OVX) mouse model. In conclusion, we constructed BEVs-BC with both bone-targeting and bone-forming in one-step using synthetic biology, which provides an effective strategy for OP and has great potential for industrialization., (© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Osteoporosis, increasingly prevalent among the aging population, poses a global health challenge. Current treatments, often limited by prolonged treatment durations, serious side effects, and suboptimal efficacy, necessitate innovative approaches. Building on previous research that highlighted the rejuvenating potential of young blood in organ vitality. This study focused on the role of exosomes and exosomal miRNA. Specifically, we investigated the efficacy of exosomes derived from young plasma (Y-Exos) in mitigating osteoporosis, contrasting them with exosomes from aged plasma (A-Exos). Our in vitro analysis involved co-culturing bone marrow mesenchymal stem cells (BMSCs) with Y-Exos or A-Exos, assessing their impact on BMSCs migration, proliferation, and osteogenic differentiation. Y-Exos exhibited a marked enhancement in BMSCs proliferation, migration, and osteogenic differentiation compared to A-Exos. Corresponding in vivo studies corroborated these findings, demonstrating that Y-Exos significantly alleviated osteoporosis, whereas A-Exos impeded bone regeneration. Furthermore, our research identified exosomal miR-217–5p as a pivotal contributor to the osteoprotective effects of Y-Exos. Our work provided a potential strategy for advancing the clinical treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP), characterized by decreased bone density and destruction of bone microstructure, is a common systemic bone disease in the elderly. Conventional therapies suffer from poor targeting and long-term toxicity. Engineered bacterial extracellular vesicles (BEVs) containing bioactive molecules show great potential as alternative OP therapies. Here, we developed a delivery system based on BEVs secreted probiotic Lactobacillus rhamnosus GG (LGG). Bone-targeting peptides were anchored on the LGG-EVs membranes, which endowed LGG-EVs the ability to deliver intrinsic miRNA to bone microenvironment. Bone-targeted LGG-EVs (BT-LGG-EVs) exhibited great bone targeting capability without significant toxicity. BT-LGG-EVs not only promoted osteogenic differentiation and mineralization but also inhibited the formation of osteoclasts. Furthermore, BT-LGG-EVs were demonstrated to be able to attenuate the OVX-induced osteoporotic phenotypes. Our study demonstrated that BT-LGG-EVs hold great promise for use as an innovative, safe, and effective solution for the treatment of OP. [ABSTRACT FROM AUTHOR]