Proanthocyanidins Inhibit Osteoblast Apoptosis via the PI3K/AKT/Bcl-xL Pathway in the Treatment of Steroid-Induced Osteonecrosis of the Femoral Head in Rats.

Abstract

BACKGROUND:

Steroid-induced osteonecrosis of the femoral head (SONFH) is a common clinical disease caused by massive or prolonged use of steroids. Its pathogenesis is unclear, but its incidence is increasing annually. It is characterized by an insidious and rapid onset, and high disability rate, causing a great burden on patients' daily life. Therefore, clarifying its pathogenesis and providing early and effective treatment for steroid osteonecrosis is important.

METHODS:

In vivo, we used methylprednisolone (MPS) to construct a SONFH rat model and employed Mirco-ct, Hematoxylin and eosin (H&E) staining, and TdT-mediated dUTP nick end labeling (TUNEL) staining analysis to evaluate the therapeutic effects of proanthocyanidins (PACs). Network pharmacology analysis was conducted to mine targets associated with femoral head necrosis, and PACs analyzed possible molecular mechanisms. In vitro, PACs were added at different doses after treatment of cells with dexamethasone (DEX), and human osteoblast-like sarcoma(MG-63) cell apoptosis was determined by Annexin V-FITC-PI. The mechanisms by which PACs regulate bone metabolism via the Phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/Recombinant Human B-Cell Leukemia/Lymphoma 2 XL(Bcl-xL) axis were explored by Western blotting.

RESULT:

In vivo studies showed that PACs prevented SONFH in rat model. The PI3K/AKT/Bcl-xL signaling pathway was selected by network pharmacology approach; in vitro studies showed that proanthocyanidin-activated AKT and Bcl-xL inhibited osteoblast apoptosis.

CONCLUSIONS:

PACs can inhibit excessive osteoblast apoptosis in SONFH via the PI3K/AKT/Bcl-xL signaling axis and have potential therapeutic effects.

• Authors: Hui Li, Yufei Zhang, Yangquan Hao, Peng Xu, Xingyu Wang, Bin Zhu, Chao Lu, Ke Xu
• Journal: Nutrients (Nutrients) Vol. 15 Issue 8 (Apr 18 2023) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 37111155 (Publication Type: Journal Article)

Chemical References

• Proto-Oncogene Proteins c-akt
• Phosphatidylinositol 3-Kinases
• Proanthocyanidins
• Methylprednisolone

Topics

• Rats
• Humans
• Animals
• Proto-Oncogene Proteins c-akt (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Femur Head (metabolism)
• Proanthocyanidins (pharmacology, therapeutic use, metabolism)
• Apoptosis
• Methylprednisolone (pharmacology)
• Osteonecrosis (chemically induced, drug therapy)
• Osteoblasts