Hyper-Activated Platelet Lysate Prevents Glucocorticoid-Induced Femoral Head Necrosis Through Autophagy

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Background: Studies have shown that platelet lysate (PL) stimulates resting osteoblasts to resume proliferation, activates the angiogenesis induction pathway, secretes factors that promote angiogenesis, accelerates osteoblast differentiation and bone formation, and can treat Avascular necrosis. Glucocorticoids(GCs) can induce osteonecrosis of the femoral head(ONFH), which is avascular osteonecrosis, which is largely related to the increase of autophagy. Super active platelet lysate (sPL) has a variety of biologically active factors, high content and strong activity. It is an upgraded version of PL and can repair ONFH. However, the relationship between sPL and glucocorticoid-related rat ONFH is still It is not clear, therefore, the purpose of our study is whether sPL can prevent and treat ONFH through autophagy. In this study, we tried to explore the role of sPL in ONFH and explore its mechanism. Methods: Through scanning electron microscopy(SEM) and enzyme-linked immunosorbent assay (ELISA) to detect the characteristics of sPL. We used methylprednisolone (MPS)-induced in vitro osteoblast necrosis model, divided into control group, MPs group, 5% group, 10% group, 15% group and 20% group, cell counting kit-8 (CCK-8), cell cycle analysis, An-nexin V And PI staining was used to diagnose its effects on cell proliferation, apoptosis, angiogenesis and osteogenesis. Using RT-PCR and western-blotting technology to analyze its molecular mechanism. Using the rat ONFH model, divided into the control group, treatment-100 group, treatment-300 group, the prevention and treatment effects of sPL on it were verified by Micro-CT and histology. Results: Increased autophagy in the ONFH model. The characterization of sPL showed that the biologically active factor was higher than that of PRP. In vitro, the results of ccK-8 showed that sPL can significantly induce the proliferation of osteoblasts and endothelial cells. Flow cytometry results also proved that sPL can inhibit cell apoptosis and promote bone formation. In addition, in the body, sPL promotes the treatment of ONFH. In order to further verify the correlation between sPL prevention and treatment of ONFH and autophagy, we found that after sPL was used to treat hormone-induced ONFH, the effect of sPL on glucocorticoid-inducedONFH by stimulating autophagy was significantly inhibited. This study reported for the first time that sPL can improve ONFH caused by glucocorticoid-activated autophagy by inhibiting the mTOR signaling pathway. which provides a research basis for the clinical application of sPL and also provides a basis for conservative treatment of femoral head necrosis. Interpretation: sPL can inhibit GC-induced ONFH through autophagy. This simple treatment brings good news for patients with femoral head necrosis. Funding: This work is supported by the Postgraduate Research & Practice Innovation Program of Harbin Medical University (No. YJSKYCX2019- 39HYD). Declaration of Interests: The authors have declared that there are no competing interests. Ethics Approval Statement: All experimental and animal care procedures were approved by the Ethics Committee of Laboratory Animal Ethics Committee of the First Affiliated Hospital of Harbin Medical University and performed under the guidelines of the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals.