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This study aims to explore the therapeutic effects of oleuropein on steroid-induced osteonecrosis of the femoral head and the molecular mechanisms involved.

May 9, 2026Scientific Reports0 citationsOpen Access

Oleuropein attenuates steroid-induced osteonecrosis of the femoral head by inhibiting osteoblast apoptosis via activation of the PI3K-AKT-Bcl2 pathway

JLJianlong LinFujian Medical University RZR ZhangFujian Medical University XLXingyu LinFujian Medical University

Key Points

This study aims to explore the therapeutic effects of oleuropein on steroid-induced osteonecrosis of the femoral head and the molecular mechanisms involved.
In vitro experiments were conducted using MC3T3-E1 osteoblasts to assess cell viability after treatment with oleuropein and methylprednisolone.
An in vivo rat model for osteonecrosis was established and treated with oleuropein, followed by analysis of bone microstructure and cell apoptosis.
Molecular mechanisms were elucidated through flow cytometry, western blotting, and network pharmacology analyses.
Oleuropein significantly reduced methylprednisolone-induced osteoblast apoptosis and improved cell viability in vitro.
In vivo studies showed oleuropein reduced empty lacunae and improved trabecular bone structure and collagen organization in SONFH rats.
Activation of the PI3K-AKT-Bcl2 pathway by oleuropein resulted in increased p-PI3K, p-AKT, and Bcl2 levels while lowering Caspase3 and Caspase9.

Abstract

teroid-induced osteonecrosis of the femoral head (SONFH) is a severe bone disorder caused by long-term glucocorticoid administration and is characterized by osteoblast apoptosis. Oleuropein (OLP), a natural compound with anti-inflammatory and antioxidant properties, has demonstrated anti-apoptotic potential in bone-related diseases. However, its therapeutic role in SONFH has not yet been elucidated. This study aimed to investigate the therapeutic effects of OLP on SONFH and elucidate its underlying molecular mechanisms. In vitro, MC3T3-E1 osteoblasts treated with methylprednisolone (MPS) were co-incubated with OLP. Cell viability was assessed using a CCK-8 assay and live/dead cell staining. In vivo, a rat SONFH model was established with lipopolysaccharide and MPS, followed by OLP treatment. Bone microstructure was analyzed by micro-computed tomography and histopathological staining (H&E, Masson, Goldner). Network pharmacology and proteomics analyses were used to identify key targets and pathways related to the effects of OLP on SONFH. Apoptosis was examined with flow cytometry, TUNEL staining and ELISA. Protein and mRNA expression levels of relevant targets and pathways were examined with western blotting and quantitative real-time polymerase chain reaction. OLP significantly reversed MPS-induced osteoblast apoptosis and enhanced cell viability. In SONFH rats, OLP reduced empty lacunae, restored trabecular bone structure, and improved collagen organization. Molecular docking confirmed OLP’s binding to AKT and Bcl2. Network pharmacology and proteomics highlighted apoptosis regulation, PI3K-AKT signaling, and cell cycle control as key mechanisms. Furthermore, OLP activated the PI3K-AKT-Bcl2 pathway, increasing p-PI3K, p-AKT, and Bcl2 levels while decreasing Caspase3 and Caspase9. OLP also promoted osteogenesis (upregulated ALP and Runx2) and angiogenesis (increased vWF and CD31). OLP alleviates SONFH by inhibiting osteoblast apoptosis and promoting osteogenesis and angiogenesis through activation of the PI3K-AKT-Bcl2 pathway. These findings support OLP as a promising natural compound for early intervention in SONFH.

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