xtracellular vesicles from mouse bone marrow macrophages-derived osteoclasts treated with zoledronic acid contain miR-146a-5p and miR-322-3p, which inhibit osteoclast function

2024 Fiscal Year Final Research Report

• Project/Area Number: 22K10230
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Tokyo Medical University
• Principal Investigator: CHIKAZU Daichi 東京医科大学, 医学部, 主任教授 (30343122)
• Co-Investigator(Kenkyū-buntansha): 落谷 孝広 東京医科大学, 医学部, 特任教授 (60192530) ; 藤居 泰行 東京医科大学, 医学部, 助教 (90829748)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: 破骨細胞 / エクソソーム / 薬剤関連顎骨壊死

Outline of Final Research Achievements

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable form of osteonecrosis of the jaw that rarely occurs in patients using bone resorption inhibitors such as bisphosphonates (BPs). Recently, the role of extracellular vesicles (EVs) in communication between osteoclasts and surrounding bone cells has been confirmed. This study aimed to elucidate the effects of EVs derived from osteoclasts treated with zoledronic acid (ZA), one of the BPs on osteoclast function. qRT-PCR analysis confirmed the amount of these specific miRNAs, with miR-146a-5p, and miR-322-3p being significantly upregulated by ZA. Overexpression of miR-146a-5p and miR-322-3p influences osteoclast differentiation, and Traf6 is a target gene of miR-146a-5p. On the other hand, Overexpression of miR-322-3p affects osteoblast differentiation. We suggest that ZA-treated osteoclast-derived EVs may play an important role in osteoclast function and bone resorption

Free Research Field

破骨細胞

Academic Significance and Societal Importance of the Research Achievements

本研究では、miR-146a-5pと322-3pが破骨細胞機能を抑制し、Traf6はmiR-146a-5pの標的遺伝子である可能性を示しました。よって、破骨細胞EV由来のmiR-146a-5pと322-3pがMRONJの発症に重要な役割を果たしていることを示唆しています。これらのmiRNAやEVは、将来的にMRONJのバイオマーカーや新規治療ターゲットとなる可能性があると考えています。