[Jintiange Capsule alleviates glucocorticoid-induced osteoporosis in rats by inhibiting vascular endothelial cell senescence and promoting bone formation].

OBJECTIVES

To investigate the role of cellular senescence in glucocorticoid-induced osteoporosis and explore the therapeutic mechanism of Jintiange (JTG) Capsule.

METHODS

Cultured human umbilical vein endothelial cells (HUVECs) and mouse pre-osteoblasts (MC3T3) were treated with methylprednisolone (MPS) or MPS combined with JTG Capsule dissolved in saline. HUVEC senescence pathways and repair capacity were analyzed using Western blotting, SA-β-Gal staining, DCFH-DA assay, scratch wound healing, and RT-PCR. The osteogenic potential of MC3T3 cells was assessed using immunofluorescence staining, ALP staining, Alizarin Red S staining, and RT-PCR. Osteoclast differentiation was evaluated by TRAP staining. Thirty 3-week-old female SD rats were randomized into control, MPS, and MPS+JTG groups, and the rats in the latter two groups received daily intraperitoneal MPS injections and treated with gavage of saline or JTG Capsule suspension for 3 months. Femurs and venous blood were collected from the rats for micro-CT analysis of femoral bone volume fraction and detection of serum bone metabolism markers.

RESULTS

Network pharmacology revealed that the active components of tiger bone had numerous intersection targets with glucocorticoid-induced osteoporosis with a strong binding affinity to cellular senescence-related targets such as P53. In MPS-treated HUVEC-derived osteoclasts, treatment with JTG Capsule significantly inhibited the expressions of P53 and P21, attenuated oxidative stress, and enhanced cell migration and angiogenic capacity. Similarly, JTG Capsule significantly enhanced osteogenic and mineralization capacities of MC3T3 cells and suppressed osteoclast differentiation. In the rat models, intraperitoneal MPS injection for 14 days resulted in significant bone loss in the femur, and JTG Capsule treatment obviously alleviated bone loss and ameliorated the disorder in serum bone metabolic markers.

CONCLUSIONS

JTG Capsule alleviates MPS-induced HUVEC senescence, enhances osteogenic capacity and suppresses osteoclastogenesis in MC3T3 cells, and promotes intraosseous angiogenesis to improve glucocorticoid-induced osteogenesis inrats.