Experimental investigation of adipose-derived mesenchymal stem cell-derived exosomes in the treatment of osteoporosis via the hsa_circ_0028877/miR-4728-3p/PTCH1 axis.

BACKGROUND

hsa_circ_0028877 may serve as a biomarker for postmenopausal osteoporosis (PMOP) based on bioinformatics analysis; nevertheless, the underlying mechanism remains ambiguous. ADSCs-derived exosomes (ADSCs-exos), as an innovative cell-free therapeutic agent that influences numerous biological processes, including immunological modulation, reduction of oxidative damage, and enhancement of tissue repair and regeneration.

OBJECTIVE

In vitro experiments were performed to evaluate the impact of hsa_circ_0028877 on cellular proliferation, osteogenic differentiation, and osteoclast differentiation. The study examined the regulatory function of ADSCs-exos on the hsa_circ_0028877/miR-4728-3p/PTCH1 axis and its therapeutic implications for osteoporosis.

METHODS

The ovariectomised rat (OVX) model was employed to simulate PMOP. The impact of hsa_circ_0028877 overexpression and knockdown on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were examined. The RNA immunoprecipitation (RIP) method was employed to validate the connection among hsa_circ_0028877, miR-4728-3p, and PTCH1. ADSCs-exos modulate their downstream molecular pathway by obstructing the nuclear transport of hsa_circ_0028877. The impact of ADSCs-exos on bone mass, trabecular microstructure, and the mineralization capacity of BMSCs was evaluated in a rat model.

RESULTS

hsa_circ_0028877 is significantly expressed in ovariectomised rat BMSCs. hsa_circ_0028877 enhances PTCH1 expression through its interaction with miR-4728-3p. ADSCs-exos can rehabilitate bone mass in the distal femur of ovariectomised rats. ADSCs-exos facilitate osteogenesis by obstructing the nuclear export of hsa_circ_0028877, significantly boosting trabecular microstructure and mineralization in the BMSCs of ovariectomised rats.

CONCLUSION

ADSCs-exos promote osteogenic differentiation and bone formation in BMSCs by obstructing the nuclear export of hsa_circ_0028877 and modulating the hsa_circ_0028877/miR-4728-3p/PTCH1 axis, thereby improving PMOP.