Identification of molecules that suppressed osteoclastgenesis in extracellular vesicles derived from osteosarcoma cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18529
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kanazawa University
• Principal Investigator: Yoshihiro Araki 金沢大学, 医学系, 協力研究員 (10800625)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 骨肉腫 / 破骨細胞 / エクソソーム / マイクロRNA / 転移

Outline of Final Research Achievements

In an orthotopic implantation study, we found that osteosarcoma-derived SEVs had the potential to enhance metastases and angiogenesis. In addition, osteosarcoma derived SEVs decreased the number of mature osteoclasts in vivo. In vitro osteoclastogenesis studies revealed that the inhibition of osteoclast maturation by osteosarcoma‐derived SEVs was mediated by suppressing the NFκB signal pathway. MicroRNA analysis of SEVs from different malignant human osteosarcomas revealed that miR-146a-5p was involved in the inhibition of osteoclastogenesis. In osteosarcoma patients, lower numbers of osteoclasts in biopsy specimens were correlated with higher malignancy. These findings indicated that osteosarcoma-derived SEVs enhance distant metastasis of osteosarcomas by inhibiting osteoclast maturation, which may be a useful prognostic marker. This diagnostic method may enable to predict malignancy at early stage, and help to provide optimal care to patients with risk of high malignancy.

Free Research Field

骨軟部腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究により，骨肉腫の進展に細胞外小胞が深く関与しており，その産生を抑えることで，腫瘍の浸潤・転移を抑えることができる可能性が示されました。今後，骨肉腫の早期発見や予後診断，新たな治療法の開発へと研究が発展することが期待されます。