A5040113122- Bone Metabolism and Diseases
- Bone health and treatments
- Adipose Tissue and Metabolism
- Bone health and osteoporosis research
- Metabolomics and Mass Spectrometry Studies
- Wnt/β-catenin signaling in development and cancer
- Connective tissue disorders research
- Cancer-related gene regulation
- Parathyroid Disorders and Treatments
- TGF-β signaling in diseases
- Regulation of Appetite and Obesity
- Bone and Dental Protein Studies
- Growth Hormone and Insulin-like Growth Factors
- Eicosanoids and Hypertension Pharmacology
- Metabolism, Diabetes, and Cancer
- Osteoarthritis Treatment and Mechanisms
- Cell Adhesion Molecules Research
- Cardiac Ischemia and Reperfusion
- Peroxisome Proliferator-Activated Receptors
- Genetic Syndromes and Imprinting
- Bone Tissue Engineering Materials
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- MicroRNA in disease regulation
- Protein Kinase Regulation and GTPase Signaling
Nagasaki University
2020-2024
Harvard University
2013-2022
Institute of Infection and Immunity
2020
Massachusetts General Hospital
2019
RELX Group (United States)
2017
Tokyo Medical and Dental University
2011-2014
Public Central Hospital of Matto Ishikawa
1994-2012
Osaka University of Pharmaceutical Sciences
2009
The University of Tokyo
2005
Montefiore Medical Center
1998
Significance Limited treatment options exist for cancer within the bone, as demonstrated by inevitable, pernicious course of metastatic breast, prostate, and blood cancers. The difficulty eliminating bone-residing necessitates novel, alternative treatments to manipulate tumor cells their microenvironment, with minimal off-target effects. To this end, we engineered bone-homing, stealth nanoparticles deliver anticancer, bone-stimulatory drugs, utility bortezomib (a model drug) multiple myeloma...
ABSTRACT Osteocytes secrete paracrine factors that regulate the balance between bone formation and destruction. Among these molecules, sclerostin (encoded by gene SOST) inhibits osteoblastic is an osteoporosis drug target. The molecular mechanisms underlying SOST expression remain largely unexplored. Here, we report histone deacetylase 5 (HDAC5) negatively regulates levels in osteocytes vitro vivo. HDAC5 shRNA increases, whereas overexpression decreases novel murine Ocy454 osteocytic cell...
Abstract Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 HDAC5, whereas stimulation RANKL, stimulator resorption, CRTC2. Salt inducible kinases (SIKs) control subcellular localization HDAC4/5 regulates both CRTC2 via phosphorylation SIK2. Like PTH, new small molecule SIK inhibitors cause decreased increased nuclear translocation mimics many the...
Osteocytes within the mineralized bone matrix control remodeling by regulating osteoblast and osteoclast activity. express aging suppressor Klotho, but functional role of this protein in skeletal homeostasis is unknown. Here we identify Klotho expression osteocytes as a potent regulator formation mass. Targeted deletion from led to striking increase volume coupled with enhanced activity, sharp contrast what observed hypomorphic (kl/kl) mice. Conversely, overexpression cultured osteoblastic...
Chondrocytes proliferate and mature into hypertrophic chondrocytes. Vascular invasion the cartilage occurs in terminal chondrocyte layer, chondrocytes die by apoptosis or transdifferentiate osteoblasts. Runx2 is essential for osteoblast differentiation maturation. -deficient mice are composed of cartilaginous skeletons lack vascular cartilage. However, requirement cartilage, mechanism transdifferentiation to osteoblasts, its significance bone development remain be elucidated. To investigate...
Irisin, a skeletal-muscle secreted myokine, facilitates muscle-bone crosstalk and skeletal remodeling in part by its action on osteoblasts osteocytes. In this study, we investigated whether irisin directly regulates osteoclasts. vitro, (2-10 ng/mL) increased osteoclast differentiation C57BL/6J mouse bone marrow progenitors; however, increase was blocked neutralizing antibody to integrin αVβ5. Irisin also resorption several substrates situ. RNAseq revealed differential gene expression induced...
Osteoblasts and adipocytes arise from a common mesenchymal precursor cell. The cell fate decision of is under the influence molecular cues signaling pathways that lead to activation or repression lineage-specific transcription factors. mechanisms determining osteoblast versus adipocyte lineage specificity in response bone morphogenic protein (BMP) remain unclear. In this study, we describe mechanism through which Zfp521 (ZNF521), regulator progression multiple immature populations, regulates...
Lactation induces bone loss to provide sufficient calcium in the milk, a process that involves osteoclastic resorption but also osteocytes and perilacunar resorption. The exact mechanisms by which contribute remain elusive. Osteocytes express genes required osteoclasts for resorption, including cathepsin K (Ctsk), lactation elevates their expression. We show Ctsk deletion prevented increase osteocyte lacunar area seen during lactation, as well effects of osteoclast numbers decrease...
Abstract BACKGROUND Expression profiles of some microRNAs (miRNAs) were associated with clinicopathological findings in human prostate cancer (PC), but the relative expression miRNAs among Gleason patterns (GPs) remains unclear. In this study, we investigated several known each GP PC. METHODS Formalin‐fixed, paraffin embedded (FFPE) tissue samples obtained from radical prostatectomy (RP) (patient set 1, n = 43, including (GP 3) 22, 4) 35, and 5) 12) needle biopsy 2, 10, 10). Cancer tissues...
Obesity during maturation can affect the growing skeleton directly and indirectly, although these effects mechanisms behind them are not fully understood. Our objective was to determine how a high-fat diet with or without metformin treatment affects skeletal development. We also sought characterize changes that occur in white adipose tissue, circulating metabolites, lipids, gut microbiota. A diet-induced obesity C57BL/6J mouse model used test of on bone using histomorphometry microcomputed...
Zinc finger-containing transcription factor Osterix/Specificity protein-7 (Sp7) is an essential for osteoblast differentiation. However, its functions in differentiated osteoblasts remain unclear and the effects of osteoblast-specific
Biphasic calcium phosphates (BCPs), consisting of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP), exhibit good biocompatibility osteoconductivity, maintaining a balance between resorption the biomaterial formation new bone. We tested whether chemical composition and/or microstructure BCPs affect osteoclasts (OCs) differentiation their ability to crosstalk with osteoblasts (OBs). To this aim, OCs were cultured on HA content 5, 20 or 60% activity assessed. found that OC is partially...
Insulin-like growth factor-1 (IGF-1) and its binding proteins are critical mediators of skeletal growth. factor-binding protein 4 (IGFBP-4) is highly expressed in osteoblasts inhibits IGF-1 actions vitro Yet, vivo studies suggest that it could potentiate IGF-2 actions. In this study, we hypothesized IGFBP-4 might the on skeleton. To test this, comprehensively studied 8- 16-week-old Igfbp4-/- mice. Both male female adult mice had marked retardation with reductions body weight, femur lengths,...
Bone morphogenic proteins (BMPs) stimulate bone formation in vivo and osteoblast differentiation vitro via a Smad signaling pathway. Recent findings revealed that the activation of nuclear factor-κB (NF-κB) inhibits BMP-induced differentiation. Here, we show NF-κB BMP by directly targeting A selective inhibitor classic pathway, BAY11–770682, enhanced BMP2-induced ectopic vivo. In mouse embryonic fibroblasts (MEFs) prepared from mice deficient p65, main subunit NF-κB, BMP2, induced...
Atypical antipsychotic (AA) drugs cause significant metabolic side effects, and clinical data are emerging that demonstrate increased fracture risk bone loss after treatment with the AA, risperidone (RIS). The pharmacology underlying adverse effects on is unknown. However, RIS action in central nervous system could be responsible because sympathetic (SNS) known to uncouple remodeling. mice significantly lowered trabecular volume fraction (bone volume/total volume), owing osteoclast-mediated...
ABSTRACT The adhesion of osteoclasts (OCs) to bone and resorption require the assembly specific F-actin structures, podosomes, their dense packing into a sealing zone. OC-specific formation zone requires interaction microtubule (MT) + ends with podosomes. Here, we deleted cofilin, cortactin (CTTN)- actin-binding protein highly expressed in OCs, determine if it acts downstream MT-CTTN axis regulate actin polymerization Conditional deletion cofilin OCs mice, driven by cathepsin K promoter...
In the brain, ventral hypothalamus (VHT) regulates energy and bone metabolism. Whether this regulation uses same or different neuronal circuits is unknown. Alteration of AP1 signaling in VHT increases expenditure, glucose utilization, density, yet specific neurons responsible for each all these phenotypes are not identified. Using neuron-specific, genetically targeted alterations as a tool adult mice, we found that agouti-related peptide-expressing (AgRP-expressing)...
ABSTRACT Human genetic evidence demonstrates that WNT1 mutations cause osteogenesis imperfecta (OI) and early-onset osteoporosis, implicating as a major regulator of bone metabolism. However, its main cellular source mechanisms action in remain elusive. We generated global limb bud mesenchymal cell–targeted deletion Wnt1 mice. Heterozygous resulted mild trabecular osteopenia due to decreased osteoblast function. Targeted progenitors led spontaneous fractures impaired function increased...
Abstract Coincubation of neutrophils with TNF inhibited the chemoattractant-directed migration under agarose and enhanced their in multiwell chemotaxis chamber. To assess physiological significance these differing vitro effects, ex vivo investigations were performed using animal models. Neutrophils from peripheral blood rabbits preadministered systemic showed impaired ability to migrate toward chemoattractants vitro. In addition, administration suppressed zymosan-activated plasma-induced...