Exploration of novel mechanism of osteoporosis focusing on resolving macrophage-derived factors.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09425
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Hokkaido University
• Principal Investigator: Takahashi Daisuke 北海道大学, 大学病院, 講師 (90528845)
• Co-Investigator(Kenkyū-buntansha): 照川 アラー 北海道大学, 医学研究院, 助教 (00723074) ; 清水 智弘 北海道大学, 大学病院, 助教 (60784246)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 骨粗鬆症 / 破骨細胞 / インターフェロンシグナル

Outline of Final Research Achievements

We explored the functional role of CLCF1 in osteoclastogenesis and bone loss associated with osteoporosis. Surprisingly, the administration of recombinant CLCF1 repressed excessive bone loss in ovariectomized mice and prevented RANKL-induced bone loss in calvarial mouse model. Likewise, the addition of recombinant CLCF1 to RANKL-stimulated monocytes resulted in a significant suppression in the number of differentiated osteoclasts in vitro. At the same dosage, CLCF1 did not exhibit any detectable negative effects on the differentiation of osteoblasts. Mechanistically, the inhibition of osteoclast differentiation by the CLCF1 treatment appears to be related to the activation of interferon signaling (IFN) and the suppression of the NF-κB signaling pathway. These collective findings point to a novel immunoregulatory function of CLCF1 in bone remodeling and highlight it as a potentially useful therapeutic agent for the treatment of osteoporosis.

Free Research Field

股関節外科　骨粗鬆症

Academic Significance and Societal Importance of the Research Achievements

骨粗鬆症と脆弱性骨折は患者ADLを著しく低下させる疾患であり、現在様々な骨粗鬆症治薬が開発・使用されているが、本邦での治療効果は十分とは言い難い。本研究では、免疫細胞であるマクロファージ由来因子が骨粗鬆症および骨微小環境内の細胞に及ぼす影響を明らかにした。免疫細胞を介した骨粗鬆症メカニズムの解析はこれまでにないアプローチであり、より有効かつ安全な骨粗鬆症治療薬開発の礎となる研究である。