A5067353567- Bone Metabolism and Diseases
- Bone health and treatments
- Inflammatory mediators and NSAID effects
- Estrogen and related hormone effects
- Protease and Inhibitor Mechanisms
- NF-κB Signaling Pathways
- Oral microbiology and periodontitis research
- Bone health and osteoporosis research
- Peptidase Inhibition and Analysis
- Pharmacological Effects of Medicinal Plants
- Vitamin D Research Studies
- Radiopharmaceutical Chemistry and Applications
- Immune Response and Inflammation
- Wound Healing and Treatments
- Periodontal Regeneration and Treatments
- Cancer, Hypoxia, and Metabolism
- Cell Adhesion Molecules Research
- TGF-β signaling in diseases
- Boron Compounds in Chemistry
- Bioactive Compounds in Plants
- Muscle Physiology and Disorders
- Dupuytren's Contracture and Treatments
- Phytoestrogen effects and research
- Blood Coagulation and Thrombosis Mechanisms
- Bone and Dental Protein Studies
Tokyo University of Agriculture and Technology
2016-2025
Waseda University
2016
Harvard University
2002-2008
Massachusetts General Hospital
2002-2008
Brigham and Women's Hospital
2005
University of Massachusetts Chan Medical School
2005
Universidad de Oviedo
2004
Tokyo University of Pharmacy and Life Sciences
2000-2003
The University of Tokyo
1997-2001
Showa University
1996-2000
As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and intravasate, they adopt a fibroblast-like phenotype engage undefined proteolytic cascades that mediate invasive activity. Herein, we find fibroblasts express an indistinguishable pericellular collagenolytic activity allows them to the ECM. Using isolated from gene-targeted mice, metalloproteinase (MMP)–dependent is identified drives invasion independently of plasminogen, gelatinase A/TIMP-2 axis, B, collagenase-3,...
Collagenase-3 (MMP13), a member of the matrix metalloproteinase (MMP) family neutral endopeptidases, is expressed in skeleton during embryonic development and highly overexpressed human carcinomas chondrocytes synovial cells rheumatoid arthritis osteoarthritis. To determine functional roles Mmp13, we generated Mmp13 -null mice that showed profound defects growth plate cartilage with markedly increased hypertrophic domains as well delay endochondral ossification formation vascularization...
PGE2 functions as a potent stimulator of bone resorption. The action is thought to be mediated by some PGE receptor subtypes present in osteoblastic cells. In this study, we examined the involvement subtypes, EP1, EP2, EP3, and EP4, PGE2-induced resorption using specific agonists for respective EPs. mouse calvaria cultures, EP4 agonist markedly stimulated resorption, but its maximal stimulation was less than that induced PGE2. EP2 also only slightly. EP1 EP3 did not stimulate it at all....
Interleukin-1 (IL-1) greatly induces osteoclast formation and stimulates bone resorption of mouse calvaria in culture. In the presence soluble IL-6 receptor (sIL-6R), similarly formation, but potency inducing organ culture is weaker than that IL-1. To study differences bone-resorbing activity between IL-1 IL-6, we examined effects two cytokines on induction matrix metalloproteinases (MMPs). calvarial cultures, markedly enhanced messenger RNA (mRNA) expression MMP-13 (collagenase 3), MMP-2...
Matrix metalloproteinases (MMPs) have been implicated in numerous tissue-remodeling processes. The finding that mice deficient collagenase-2 (MMP-8) are more susceptible to develop skin cancer, prompted us investigate the role of this protease cutaneous wound healing. We observed a significant delay closure MMP8−/− and an altered inflammatory response their wounds, with neutrophil infiltration during first days persistent inflammation at later time points. These changes were accompanied by...
Abstract Osteoclasts differentiate from the hemopoietic monocyte/macrophage cell lineage in bone marrow through cell-cell interactions between osteoclast progenitors and stromal/osteoblastic cells. Here we show another differentiation pathway closely connected with B lymphocyte differentiation. Recently TNF family molecule factor/receptor activator of NF-κB ligand (ODF/RANKL) was identified as a key membrane-associated factor regulating We demonstrate that B-lymphoid cells are major source...
Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss due to stimulated resorption osteoclasts. During our investigations of the pathogenesis estrogen deficiency, we found that OVX selectively stimulates B-lymphopoiesis which accumulation B220-positive pre-B cells mouse marrow. To examine possible correlation between and loss, 8-week-old female mice were treated with interleukin (IL) 7, We also examined mass IL-7 receptor-knockout exhibit suppression The increased...
Interstitial collagen plays a crucial structural role in arteries. Matrix metalloproteinases (MMPs), including MMP-13/collagenase-3, likely contribute to catabolism atherosclerotic plaques.To test the hypothesis that specific MMP-collagenase influences development and structure of plaques, this study used atherosclerosis-susceptible apolipoprotein E-deficient mice lack MMP-13/collagenase-3 (Mmp-13(-/-)/apoE(-/-)) or express wild-type (Mmp-13(+/+)/apoE(-/-)). Both groups consumed an...
Prostaglandin E(2) (PGE(2)) acts as a potent stimulator of bone resorption. In this study, we first clarified in normal ddy mice the involvement protein kinase A and induction matrix metalloproteinases (MMPs) PGE(2)-induced resorption, then identified PGE receptor subtype(s) mediating PGE(2) action using lacking each subtype (EP1, EP2, EP3, EP4) receptor. calvarial culture obtained from mice, both dibutyryl cyclic AMP (Bt(2)cAMP) stimulated resorption induced MMPs including MMP-2 MMP-13....
Extracellular matrix production and degradation by bone cells are critical steps in metabolism. Mutations of the gene encoding MMP-2, an extracellular matrix-degrading enzyme, associated with a human genetic disorder characterized subcutaneous nodules, arthropathy, focal osteolysis. It is not known how loss MMP-2 function results pathology. Here, we show that Mmp2(-/-) mice exhibited opposing phenotypes caused impaired osteocytic canalicular network. showed decreased mineral density limb...
Prostaglandin E (PGE)2 produced by osteoblasts acts as a potent stimulator of bone resorption. Inflammatory loss is accompanied osteoclast formation induced bone-resorbing cytokines, but the mechanism PGE2 production and resorption in vivo not fully understood. Using cytosolic phospholipase A2α (cPLA2α)-null mice, we examined role cPLA2α synthesis In marrow cultures, interleukin (IL)-1 markedly stimulated wild-type cPLA2α-null mice. Osteoblastic stromal cells expression cyclooxygenase...
PGE(2) acts as a potent stimulator of bone resorption in several disorders including osteoarthritis and periodontitis. Three PGE synthases (PGES) were isolated for production, but which PGES has the major role inflammatory is still unclear. In this study, we examined LPS-induced using membrane-bound (mPGES)-1-deficient mice (mPges1(-/-)). osteoblasts from wild-type mice, production was greatly stimulated by LPS following expression cyclooxygenase 2 mPGES-1 mRNA, whereas no found mPges1(-/-)....
Proteinases play a pivotal role in wound healing by regulating cell-matrix interactions and availability of bioactive molecules. The matrix metalloproteinase-13 (MMP-13) granulation tissue growth was studied subcutaneously implanted viscose cellulose sponge MMP-13 knockout (Mmp13(-/-)) wild type (WT) mice. samples were harvested at time points day 7, 14 21 subjected to histological analysis gene expression profiling. Granulation significantly reduced (42%) Mmp13(-/-) mice showed delayed...
Abstract Spaceflight is known to induce severe systemic bone loss and muscle atrophy of astronauts due the circumstances microgravity. We examined influence artificially produced 2G hypergravity on mice for mass with newly developed centrifuge device. also analyzed effects microgravity (mostly 0G) artificial 1G in ISS (international space station) mouse mass. Experiment ground, humerus, femur tibia was measured using micro-computed tomography (μCT), all significantly increased compared...
MMPs, which degrade components of the ECM, have roles in embryonic development, tissue repair, cancer, arthritis, and cardiovascular disease. We show that a missense mutation MMP13 causes Missouri type human spondyloepimetaphyseal dysplasia (SEMD(MO)), an autosomal dominant disorder characterized by defective growth modeling vertebrae long bones. Genome-wide linkage analysis mapped SEMD(MO) to 17-cM region on chromosome 11q14.3-23.2 contains cluster 9 MMP genes. Among these, represented best...
Bone metastasis of breast cancer induces severe osteolysis with increased bone resorption. Osteoclast differentiation regulated by the receptor activator NF-kappaB ligand (RANKL) in osteoblasts and matrix degradation induced metalloproteinases (MMPs) are thought to be involved process When nude mice were inoculated human cells, MDA-MB-231(MDA-231), numerous osteoclasts resorbed markedly progressed femur tibia MDA-231 tumour. The expression RANKL, MMP-13 membrane-type 1-MMP mRNA was elevated...
Epigallocatechin gallate (EGCG), a major polyphenol in green tea, possesses antioxidant properties and regulates various cell functions. Here, we examined the function of EGCG inflammatory bone resorption. In calvarial organ cultures, lipopolysaccharide (LPS)‐induced resorption was clearly suppressed by EGCG. osteoblasts, LPS‐induced expression COX‐2 mPGES‐1 mRNAs, as well prostaglandin E2 production, also RANKL expression, which is essential for osteoclast differentiation. mandibular...
Abnormalities of bone turnover are commonly observed in patients with chronic kidney disease (CKD), and the low-turnover is considered to be associated low serum parathyroid hormone (PTH) levels skeletal resistance PTH. Indoxyl sulfate (IS) a representative uremic toxin that accumulates blood CKD. Recently, we have reported IS exacerbates induced by parathyroidectomy (PTX) adult rats, suggested directly induces through inhibition formation mechanisms unrelated To define direct action...