A5065427229- Cancer-related molecular mechanisms research
- Osteoarthritis Treatment and Mechanisms
- MicroRNA in disease regulation
- Tendon Structure and Treatment
- RNA Research and Splicing
- Circular RNAs in diseases
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Genomics and Chromatin Dynamics
- Muscle Physiology and Disorders
- Cancer-related gene regulation
- Knee injuries and reconstruction techniques
- interferon and immune responses
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Rheumatoid Arthritis Research and Therapies
- Cellular Mechanics and Interactions
- NF-κB Signaling Pathways
- CRISPR and Genetic Engineering
- Bone Metabolism and Diseases
- Animal Genetics and Reproduction
- Cell Adhesion Molecules Research
- Spaceflight effects on biology
- Developmental Biology and Gene Regulation
- Exercise and Physiological Responses
Tokyo Medical and Dental University
2016-2025
Scripps Research Institute
2015-2025
Tokyo University of Science
2025
Torrey Pines Institute For Molecular Studies
2022-2024
Scripps (United States)
2020-2024
Scripps Institution of Oceanography
2020-2024
Institute of Science Tokyo
2024
The University of Tokyo
2020-2022
National Center For Child Health and Development
2011-2020
Japan Agency for Medical Research and Development
2016-2020
Abstract Objective Several microRNA, which are ∼22‐nucleotide noncoding RNAs, exhibit tissue‐specific or developmental stage–specific expression patterns and associated with human diseases. The objective of this study was to identify the pattern microRNA‐146 (miR‐146) in synovial tissue from patients rheumatoid arthritis (RA). Methods miR‐146 5 RA, osteoarthritis (OA), 1 normal subject analyzed by quantitative reverse transcription–polymerase chain reaction (RT‐PCR) situ hybridization...
Osteoarthritis (OA), the most prevalent aging-related joint disease, is characterized by insufficient extracellular matrix synthesis and articular cartilage degradation, mediated several proteinases, including Adamts-5. miR-140 one of a very limited number noncoding microRNAs (miRNAs) specifically expressed in cartilage; however, its role development and/or tissue maintenance largely uncharacterized. To examine function homeostasis, we generated mouse line through targeted deletion miR-140....
Abstract Objective MicroRNA (miRNA) are a class of noncoding small RNAs that act as negative regulators gene expression. MiRNA exhibit tissue‐specific expression patterns, and changes in their may contribute to pathogenesis. The objectives this study were identify miRNA expressed articular chondrocytes, determine osteoarthritic (OA) cartilage, address the function miRNA‐140 (miR‐140). Methods To specifically we performed profiling using microarrays quantitative polymerase chain reaction with...
We describe a molecular switch based on the controlled methylation of nucleosome and transcriptional cofactors, CREB-binding proteins (CBP)/p300. The CBP/p300 site is localized to an arginine residue that essential for stabilizing structure KIX domain, which mediates CREB recruitment. Methylation by coactivator-associated methyltransferase 1 (CARM1) blocks activation disabling interaction between kinase inducible domain (KID) CREB. Thus, CARM1 functions as corepressor in cyclic adenosine...
Abstract Objective A role of microRNA, which are ∼22‐nucleotide noncoding RNAs, has recently been recognized in human diseases. The objective this study was to identify the expression pattern microRNA‐146a (miR‐146a) cartilage from patients with osteoarthritis (OA). Methods miR‐146a 15 OA analyzed by quantitative reverse transcription–polymerase chain reaction (RT‐PCR) and situ hybridization. Induction cultures normal articular chondrocytes following stimulation interleukin‐1β (IL‐1β)...
Mohawk ( Mkx ) is a member of the Three Amino acid Loop Extension superclass atypical homeobox genes that expressed in developing tendons. To investigate vivo functions Mkx, we generated −/− mice. These mice had hypoplastic tendons throughout body. Despite reduction tendon mass, cell number tail fiber bundles was similar between wild-type and We also observed small collagen fibril diameters down-regulation type I data indicate plays critical role differentiation by regulating production cells.
Abstract Introduction Recent findings suggest that articular cartilage contains mesenchymal progenitor cells. The aim of this study was to examine the distribution stem cell markers (Notch-1, Stro-1 and VCAM-1) molecules modulate differentiation (Notch-1 Sox9) in normal adult human osteoarthritis (OA) cartilage. Methods Expression analyzed by immunohistochemistry (IHC) flow cytometry. Hoechst 33342 dye used identify sort side population (SP). Multilineage assays including chondrogenesis,...
Aging is a main risk factor for osteoarthritis (OA). FoxO transcription factors protect against cellular and organismal aging, expression in cartilage reduced with aging OA. To investigate the role of cartilage, Col2Cre-FoxO1, 3, 4 single knockout (KO) triple KO mice (Col2Cre-TKO) were analyzed. Articular Col2Cre-TKO Col2Cre-FoxO1 was thicker than control at 1 or 2 months age. This associated increased proliferation chondrocytes vivo vitro. OA-like changes developed synovium, subchondral...
Introducing a point mutation is fundamental method used to demonstrate the roles of particular nucleotides or amino acids in genetic elements proteins and widely vitro experiments based on cultured cells exogenously provided DNA. However, vivo application this approach by modifying genomic loci uncommon, partly due its technical temporal demands. This leaves many findings un-validated under conditions. We herein applied CRISPR/Cas9 system generate mice with mutations their genomes, which led...
Lysosomal stress due to the accumulation of nucleic acids (NAs) activates endosomal TLRs in macrophages. Here, we show that lysosomal RNA stress, caused by lack RNase T2, induces macrophage multiple organs such as spleen and liver through TLR13 activation microbiota-derived ribosomal RNAs. triggered emergency myelopoiesis, increasing number myeloid progenitors bone marrow spleen. Splenic macrophages continued proliferate mature into expressing anti-inflammatory cytokine IL-10. In liver,...
The transcriptional activation by SRY-type high mobility group box 9 (SOX9) and the transforming growth factor beta (TGF-beta) signals are necessary for chondrogenic differentiation. We have previously shown that CREB-binding protein (CBP/p300) act as an important SOX9 co-activator during chondrogenesis. In present study, we investigated relationship between TGF-beta-dependent Smad2/3 signaling pathways SOX9-CBP/p300 complex at early stage of Overexpressed Smad3 strongly induced primary...
Abstract Objective To examine whether depsipeptide (FK228), a histone deacetylase (HDA) inhibitor, has inhibitory effects on the proliferation of synovial fibroblasts from rheumatoid arthritis (RA) patients, and to systemic administration FK228 in an animal model arthritis. Methods Autoantibody‐mediated (AMA) was induced 19 male DBA/1 mice (6–7 weeks old); 10 them were treated by intravenous (2.5 mg/kg), 9 used as controls. The examined radiographic, histologic, immunohistochemical analyses...
Chondrocytes are critical components for the precise patterning of a developing skeletal framework and articular joint formation. Sox9 is key transcription factor that essential chondrocyte differentiation chondrocyte-specific gene expressions; however, transcriptional activation mechanism not fully understood. Here we demonstrate utilizes cAMP-response element-binding protein (CREB)-binding (CBP)/p300 to exert its effects. associates with CBP/p300 in chondrosarcoma cell line SW1353 via...
Muscle atrophy is caused by accelerated protein degradation and occurs in many pathological states. Two muscle-specific ubiquitin ligases, MAFbx/atrogin-1 muscle RING-finger 1 (MuRF1), are prominently induced during mediate atrophy-associated degradation. Blocking the expression of these two ligases provides protection against atrophy. Here we report that miR-23a suppresses translation both MuRF1 a 3'-UTR-dependent manner. Ectopic sufficient to protect muscles from vitro vivo. Furthermore,...