A5021981750- Melanoma and MAPK Pathways
- Bone Metabolism and Diseases
- Glioma Diagnosis and Treatment
- Amino Acid Enzymes and Metabolism
- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- Ubiquitin and proteasome pathways
- Bone health and treatments
- TGF-β signaling in diseases
- Regulation of Appetite and Obesity
- NF-κB Signaling Pathways
- Adipose Tissue and Metabolism
- FOXO transcription factor regulation
- Cancer, Hypoxia, and Metabolism
- Cytokine Signaling Pathways and Interactions
- Protein Degradation and Inhibitors
- Cancer-related Molecular Pathways
- Osteoarthritis Treatment and Mechanisms
- Kruppel-like factors research
- Exercise and Physiological Responses
- Mesenchymal stem cell research
- Autophagy in Disease and Therapy
- Mast cells and histamine
- Glycosylation and Glycoproteins Research
- Microtubule and mitosis dynamics
Columbia University Irving Medical Center
2025
Gifu Pharmaceutical University
2019-2024
Pharmac
2019-2020
Kanazawa University
2015-2020
ABSTRACT We have previously shown that endochondral ossification is finely regulated by the Clock system expressed in chondrocytes during postnatal skeletogenesis. Here we show a sophisticated modulation of bone resorption and mass through its expression bone-forming osteoblasts. Brain muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1) Period1 (Per1) were with oscillatory rhythmicity vivo, circadian rhythm was also observed cultured osteoblasts Per1::luciferase...
Glioma stem cells (GSCs) contribute to the pathogenesis of glioblastoma (GBM), which is most malignant form glioma. The implications and underlying mechanisms protein glycosylation in GSC phenotypes GBM malignancy are not fully understood. implication corresponding candidate genes on cell properties GSCs poor clinical outcomes were investigated, using datasets from Gene Expression Omnibus, Cancer Genome Atlas, Chinese accompanied by biological validation vitro. N-linked was significantly...
Activating transcription factor 3 (Atf3) has been implicated in the pathogenesis of various diseases, including cancer and inflammation, as well regulation cell proliferation differentiation. However, involvement Atf3 developmental skeletogenesis joint disease not studied to date. Here, we show that is a critical mediator osteoarthritis (OA) development through its expression chondrocytes. ATF3 was markedly up-regulated OA cartilage both mice humans. Conditional deletion chondrocytes did...
Bone marrow mesenchymal stem cells (MSCs) are critical regulators of postnatal bone homeostasis. Osteoporosis is characterized by volume and strength deterioration, partly due to MSC dysfunction. Cyclin-dependent kinase 8 (CDK8) belongs the transcription-related CDK family. Here, CDK8 in MSCs was identified as important for level increased aged along with association aging-related signals. Mouse genetic studies revealed that plays a crucial role resorption Mechanistically, extrinsically...
The mechanistic/mammalian target of rapamycin (mTOR) is widely implicated in the pathogenesis various diseases, including cancer, obesity, and cardiovascular disease. Bone homeostasis maintained by actions bone-resorbing osteoclasts bone-forming osteoblasts. An imbalance sophisticated regulation osteoblasts leads to as well etiology certain metabolic bone osteoporosis osteopetrosis. Here, we identified mTOR complex 1 (mTORC1) a pivotal mediator resorption under pathological conditions...
Amino acid uptake through the transporter LAT1 maintains bone homeostasis by stimulating mTORC1 signaling.
Abstract Glioma stem cells (GSCs) contribute to the pathogenesis of glioblastoma, most malignant form glioma. The implication and underlying mechanisms SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) on GSC phenotypes remain unknown. We previously demonstrated that SMURF2 phosphorylation at Thr 249 (SMURF2 Thr249 ) activates its activity. Here, we demonstrate plays an essential role in maintaining stemness tumorigenicity. silencing augmented self-renewal potential tumorigenicity...
Extracellular signal-regulated kinase 5 (Erk5) belongs to the mitogen-activated protein (MAPK) family. Previously, we demonstrated that Erk5 directly phosphorylates Smad-specific E3 ubiquitin ligase 2 (Smurf2) at Thr249 (Smurf2Thr249) activate its activity. Although have clarified importance of in embryonic mesenchymal stem cells (MSCs) on skeletogenesis, role adult bone marrow (BM)-MSCs homeostasis remains unknown. Leptin receptor-positive (LepR+) BM-MSCs represent a major source and are...
Abstract Bone homeostasis is maintained by the sophisticated coupled actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Here we identify activating transcription factor 3 (ATF3) as a pivotal for regulation bone resorption remodeling under pathological condition through modulating proliferation osteoclast precursors. The precursor-specific deletion ATF3 in mice led to prevention receptor activator nuclear factor-κB (RANK) ligand (RANKL)-induced loss, although neither volume...
ABSTRACT Erk5 belongs to the mitogen-activated protein kinase (MAPK) family. Following its phosphorylation by Mek5, modulates several signaling pathways in a number of cell types. In this study, we demonstrated that inactivation mesenchymal cells causes abnormalities skeletal development inducing Sox9, an important transcription factor skeletogenesis. We further demonstrate directly phosphorylates and activates Smurf2 (a ubiquitin E3 ligase) at Thr249, which promotes proteasomal degradation...
ABSTRACT Bone homeostasis is maintained by the synergistic actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Although interferon-related developmental regulator 1 (Ifrd1) has been identified as a transcriptional coactivator/repressor in various cells, little attention paid to its role osteoblastogenesis bone thus far. Here, we show that Ifrd1 critical mediator both cell-autonomous regulation osteoblast-dependent osteoclastogenesis. Osteoblast-specific deletion murine...
The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) regulates cellular function in various cell types. Although the role mTORC1 skeletogenesis has been investigated previously, here we show a critical mTORC1/4E-BPs/SOX9 axis regulating through its expression undifferentiated mesenchymal cells. Inactivation Raptor, component mTORC1, limb buds before condensations resulted marked loss both cartilage and bone. Mechanistically, demonstrated that selectively controls RNA translation...
Bone homeostasis is maintained by the synergistic actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Here, we show that transcriptional coactivator/repressor interferon-related developmental regulator 1 (Ifrd1) expressed in osteoclast lineages represents a component machinery regulates bone homeostasis. Ifrd1 expression was transcriptionally regulated preosteoclasts receptor activator nuclear factor κB (NF-κB) ligand (RANKL) through protein 1. Global deletion murine...
Glioma stem cells (GSC) promote the malignancy of glioblastoma (GBM), most lethal brain tumor. ERK5 belongs to MAPK family. Here, we demonstrated that kinase 5 (MEK5)-ERK5-STAT3 pathway plays an essential role in maintaining GSC stemness and tumorigenicity by integrating genetic pharmacologic manipulation RNA sequencing analysis clinical specimens. was highly expressed activated GSCs. silencing short hairpin GSCs suppressed self-renewal potential GBM malignant growth concomitant with...
Sympathetic tone activates the function of classical brown adipocytes, which constitutively exist in adipose tissue (BAT), and inducible adipocytes (so-called beige adipocytes), sporadically reside within white (WAT). Here we identified transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) as a negative thermogenic mitochondrial gene expression adipocytes. Ifrd1 was markedly induced by cold exposure administration CL-316243 (a β3 adrenergic agonist) interscapular...
Hypothalamic neurons regulate body homeostasis by sensing and integrating changes in the levels of key hormones primary nutrients (amino acids, glucose, lipids). However, molecular mechanisms that enable hypothalamic to detect remain elusive. Here, we identified l-type amino acid transporter 1 (LAT1) leptin receptor-expressing (LepR-expressing) as being important for systemic energy bone homeostasis. We observed LAT1-dependent uptake hypothalamus, which was compromised a mouse model obesity...
Osteoarthritis (OA) is the most common degenerative and progressive joint disease. Cellular senescence an irreversible cell cycle arrest with age, while protein glycosylation abundant post-translational modification, regulating various cellular biological pathways. The implication of either chondrocyte or in OA pathogenesis has been extensively individually studied. In this study, we aimed to investigate possible relationship between on using single-cell RNA sequencing datasets clinical...
β-Cryptoxanthin, which is primarily obtained from citrus fruits such as Satsuma mandarins, a major carotenoid routinely found in human serum. Recently, we demonstrated that daily oral intake of β-cryptoxanthin prevented ovariectomy-induced bone loss and ameliorated neuropathic pain mice. Although exerts preventive effects on various lifestyle-related diseases, there have been no studies the effect development osteoarthritis, most common degenerative joint disease, frequently leads to ability...
Abstract Extracellular signal-regulated kinase 5 (Erk5), a member of the MAPK family, is specifically phosphorylated and activated by MAPK/Erk kinase-5. Although it has been implicated in odor discrimination long-term memory via its expression central nervous system, little known regarding physiological importance neuronal Erk5 body weight energy homeostasis. In current study, systemic insulin injection significantly induced phosphorylation hypothalamus. Moreover, deficiency leptin receptor...
The availability of amino acid in the brown adipose tissue (BAT) has been shown to be altered under various conditions; however, little is known about possible expression and pivotal role transporters BAT physiological pathological conditions. present study comprehensively investigated whether are regulated by obesogenic conditions vivo. Moreover, we mechanism underlying regulation stressors adipocytes vitro. solute carrier family 38 member 1 (Slc38a1; gene encoding sodium-coupled neutral...
We previously demonstrated a marked upregulation in the bone morphogenic protein (BMP)/growth differentiation factor (GDF) family member, GDF5, which is capable of promoting brown adipogenesis, adipose tissue (BAT) obese mice. In this study, we identified other GDF members, besides GDF5 that are responsive to different obesogenic signals BAT using inborn and acquired obesity animal models. from leptin-deficient ob/ob mice, GDF1 expression was preferentially downregulated, whereas several...
β-cryptoxanthin, a xanthophyll carotenoid, exerts preventive effects on various lifestyle-related diseases. Here, we found that daily oral administration of β-cryptoxanthin significantly ameliorated the development tactile allodynia following spinal nerve injury but was ineffective in mechanical an inflammatory pain model mice. Our results suggest supplementation would be beneficial for prophylaxis neuropathic pain.