AB0639 EXOSOMES DERIVED FROM ENDOTHELIAL CELLS PREVENT OSTEOBLAST APOPTOSIS IN STEROID-INDUCED OSTEONECROSIS OF THE FEMORAL HEAD RAT MODEL VIA THE PI3K/AKT/Bcl-2 SIGNAL PATHWAY
Authors: J. Sun, W. Zheng, Y. Zhang, Z. Gu
Journal: Annals of the Rheumatic Diseases (2021)

Background: Osteonecrosis of the femoral head (ONFH) is a common disease caused by many trauma factors and un-trauma factors. Among those un-trauma factors, steroid-induced osteonecrosis of the femoral head (SNFH) accounted for a large proportion and mainly concentrated in young people. SNFH has been reported as an irreversible disease and associated with the damage of blood vessels and the loss balance of bone homeostasis. Circulating endothelial progenitor cells (CEPCs), one part of circulating endothelial cells (CECs), are immature precursor cells with proliferative potential. The damage of vascular endothelial cells in SNFH has been confirmed by many studies, but the changes of CECs and CEPCs in the peripheral blood of patients with SNFH have not been studied yet. Objectives: The objective of the study is to explore the number of CECs and CEPCs in SNFH patients and normal people and then investigate whether EC-secreted exosomes (EC-exos) could prevent the progression of SNFH in rat model and its mechanism of action. Methods: We collect peripheral blood of 3 SNFH patients and 3 heathy people and detected the levels of CECs and CEPCs by Flow cytometer. TEM, NTA and western blot was used to characterize the isolated EC-exos. Annexin V-FITC/PI double staining with flow cytometric analysis and western blot were used to evaluate MC3T3-E1 cells apoptosis. CCK-8, scratching experiment and transwell were used to evaluate MC3T3-E1 cells viability and migration ability. Micro-CT and morphological staining were used to evaluate the progress of SNFH in rat model. Results: Firstly, we found that the number of CECs and CEPCs in the peripheral blood was decreased in SNFH patients than normal people. Then our results indicated that EC-exos could improve the migration, viability and prevent apoptosis of osteoblasts under dexamethasone by activating the PI3K/AKT/Bcl-2 signal pathway in vitro. Finally, our Micro-CT and morphological staining results in SNFH rat model revealed that EC-exos prevented the progression of SNFH. Conclusion: EC-exos could enhance the cell viability and migration ability of osteoblasts under dexamethasone and play an anti-apoptosis role against steroids-induced osteoblast apoptosis by activating the PI3K/AKT/Bcl-2 signal pathway. EC-exos prevented the progression of SNFH in rat model. References: [1]Zalavras CG, Lieberman JR. Osteonecrosis of the femoral head: evaluation and treatment. J Am Acad Orthop Surg. 2014;22(7):455-64. [2]Microsurgery Department of the Orthopedics Branch of the Chinese Medical Doctor A, Group from the O, Bone Defect Branch of the Chinese Association of R, Reconstructive S, Microsurgery, Reconstructive Surgery Group of the Orthopedics Branch of the Chinese Medical A. Chinese Guideline for the Diagnosis and Treatment of Osteonecrosis of the Femoral Head in Adults. Orthop Surg. 2017;9(1):3-12. [3]Mont MA, Jones LC, Hungerford DS. Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am. 2006;88(5):1117-32. [4]Yuan HF, Zhang J, Guo CA, Yan ZQ. Clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation: a meta-analysis of seven case-control studies. Clinics (Sao Paulo). 2016;71(2):110-3. [5]Houdek MT, Wyles CC, Packard BD, Terzic A, Behfar A, Sierra RJ. Decreased Osteogenic Activity of Mesenchymal Stem Cells in Patients With Corticosteroid-Induced Osteonecrosis of the Femoral Head. J Arthroplasty. 2016;31(4):893-8. Disclosure of Interests: None declared.