Effects and Mechanisms of Bone Polypeptide on Improving Osteoporosis in Ovariectomized Rats via Regulation of Autophagy and Apoptosis

Objective: To investigate whether bone polypeptide (GDT) exerts protective effects against osteoporosis in rats through autophagy and apoptosis pathways. Methods: A postmenopausal osteoporosis rat model (POMP) was established via ovariectomy. Rats were randomly divided into Sham-operated, model, diethylstilbestrol (25 μg/kg), and GDT low-, medium-, and high-dose groups (50, 100, 200 mg·kg−1). Intragastric administration was performed for 90 days post-surgery. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Bone biomechanical properties were evaluated via three-point bending tests. Bone microstructure was analyzed by morphometry. Serum bone metabolism markers were detected using enzyme-linked immunosorbent assay (ELISA). mRNA and protein expressions of autophagy-related genes (p62, Beclin-1, LC3-II) and apoptosis-related genes (Caspase-3, Caspase-9, BAX, Bcl-2) were determined by RT-qPCR and Western blot. Results: GDT significantly increased calcium, magnesium, phosphorus, and hydroxyproline contents in bone tissues (PP−1 dose range, GDT activated the autophagy pathway and inhibited apoptosis. mRNA and protein expressions of p62 were down regulated, while Beclin-1 and LC3-II were upregulated. Expressions of BAX, Caspase-3, and Caspase-9 were reduced, whereas Bcl-2 was increased. Significant differences were observed in the high-dose group compared to the model group (PPBeclin-1/LC3-II axis and inhibiting mitochondrial apoptosis via the Bcl-2/BAX-Caspase cascade. This study provides a novel strategy for targeted osteoporosis therapy.