東京大学 · Medicine
Sakae Tanaka 교수의 연구실은 골다공증 및 골병변과 관련된 면역세포, 특히 옥시클라스트의 발달과 기능 조절 메커니즘을 중심으로 연구를 진행하고 있습니다. 특히 M-CSF와 RANKL를 중심으로 한 신호전달 경로, 세포 분화 조절에 관여하는 전사 인자(NFATc1)의 에피제네틱 조절 메커니즘, 그리고 MMP14와 ADAM10 같은 단백질 분해효소가 RANKL를 어떻게 조절하는지에 대한 분자 기전을 규명하고 있습니다. 또한 c-Cbl과 같은 신호전달 단백질의 인산화 조절 메커니즘을 통해 면역세포 기능 조절의 분자 기초를 탐색하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
The mechanism of action of macrophage colony-stimulating factor (M-CSF) in osteoclast development was examined in a co-culture system of mouse osteoblastic cells and spleen cells. In this co-culture, osteoclast-like multinucleated cells (MNCs) were formed within 6 d in response to 10 nM 1 alpha,25(OH)2D3 added only for the final 2 d of culture. Simultaneously adding hydroxyurea for the final 2 d completely inhibited proliferation of cultured cells without affecting 1 alpha,25(OH)2D3-stimulated M
Osteoclasts are primary cells for physiological and pathological bone resorption, and receptor activator of nuclear factor-kappaB ligand (RANKL) is critically involved in the differentiation, activation, and survival of these cells. Recently, therapeutics for pathological bone destruction targeting RANKL pathways has attracted a great deal of attention. Herein, we review the recent advances in the research on osteoclast biology and discuss the advantages and disadvantages of anti-RANKL therapies
Receptor activator of NF-kappaB ligand (RANKL) is a transmembrane glycoprotein that has an essential role in the development of osteoclasts. The extracellular portion of RANKL is cleaved proteolytically to produce soluble RANKL, but definite RANKL sheddase(s) and the physiologic function of RANKL shedding have not yet been determined. In the present study, we found that matrix metalloproteinase (MMP) 14 and a disintegrin and metalloproteinase (ADAM) 10 have strong RANKL shedding activity. In Wes
The c-cbl protooncogene product (c-Cbl) is a 120-kDa protein that has been shown to bind to the Src homology 3 domains of various proteins, suggesting its involvement in signal transduction pathways. We identified one of the most prominent tyrosine-phosphorylated proteins in Fcγ receptor (FcγR)-stimulated macrophages to be c-Cbl. Tyrosine phosphorylation of c-Cbl occurred within 20 s after stimulation and reached maximum levels within 3-5 min. c-Cbl was also tyrosine-phosphorylated in epidermal
Gene expression is controlled by epigenetic mechanisms such as histone acetylation and methylation, and recent studies have revealed that key developmental steps are regulated by the trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3). Using ChIP sequencing technology combined with real-time PCR, we here demonstrate that the H3K27me3 observed in the Nfatc1 gene in bone marrow-derived macrophages (BMMs) was markedly reduced in mature osteoclasts. Jumonji domain-containing 3 (
