A5017928696- Bone Metabolism and Diseases
- Bone health and treatments
- Bone health and osteoporosis research
- Bone and Dental Protein Studies
- Connective tissue disorders research
- Growth Hormone and Insulin-like Growth Factors
- Cytokine Signaling Pathways and Interactions
- Tendon Structure and Treatment
- TGF-β signaling in diseases
- Vitamin D Research Studies
- Genetic Syndromes and Imprinting
- RNA Research and Splicing
- Cellular Mechanics and Interactions
- Muscle Physiology and Disorders
- Lipoproteins and Cardiovascular Health
- dental development and anomalies
- Knee injuries and reconstruction techniques
- Bone Tissue Engineering Materials
- Lipid metabolism and disorders
- Wnt/β-catenin signaling in development and cancer
- Calcium signaling and nucleotide metabolism
- Cholesterol and Lipid Metabolism
- Osteoarthritis Treatment and Mechanisms
- Signaling Pathways in Disease
- Proteoglycans and glycosaminoglycans research
Tokyo Medical and Dental University
2015-2024
Teikyo Heisei University
2023-2024
The University of Tokyo
2022-2023
Teikyo University
2020
University of Wisconsin–Madison
2015
Medical Research Institute
2011-2014
Center for Global Health
2012
Nippon Medical School
2001-2007
Thomas Jefferson University
2000-2006
Japan Society for the Promotion of Science
2006
Abstract Tendon function involves the development of an organized hierarchy collagen fibrils. Small leucine‐rich proteoglycans have been implicated in regulation fibrillogenesis and decorin is prototypic member this family. Decorin‐deficient mice demonstrate altered fibril structure mechanical mature skin tail tendons. However, developmental role(s) needs to be elucidated. To define these during tendon development, tendons (flexor digitorum longus) were analyzed ultrastructurally from...
Collagen fibrillogenesis is finely regulated during development of tissue-specific extracellular matrices. The role(s) a leucine-rich repeat protein subfamily in the regulation tendon were defined. Lumican-, fibromodulin-, and double-deficient mice demonstrated disruptions fibrillogenesis. With development, amount lumican decreases to barely detectable levels while fibromodulin increases significantly, these changing patterns may regulate this process. Electron microscopic analysis...
Lumican and fibromodulin regulate the assembly of collagens into higher order fibrils in connective tissues. Here, we show that mice deficient both these proteoglycans manifest several clinical features Ehlers-Danlos syndrome. TheLum −/− Fmod are smaller than their wild type littermates display gait abnormality, joint laxity, age-dependent osteoarthritis. Misaligned knee patella, severe dysmorphogenesis, extreme tendon weakness likely causes for laxity double-nulls. Fibromodulin deficiency...
Abstract Mesenchymal stem cells (MSCs) can be obtained from various tissues, and contain common features. However, an increasing number of reports have described variant properties dependent cell sources. We examined (1) whether MSCs existed in several intraarticular (2) gene expression profiles tissue closely resembled each other, (3) identified genes were specific to MSCs. Human synovium, meniscus, ligament, muscle, adipose tissue, bone marrow harvested, colony‐forming analyzed. All these...
Osteoporosis is one of the major health problems in our modern world. Especially, disuse (unloading) osteoporosis occurs commonly bedridden patients, a population that rapidly increasing due to aging-associated diseases. However, mechanisms underlying such unloading-induced pathological bone loss have not yet been fully understood. Since sympathetic nervous system could control mass, we examined whether controlled by tone. Treatment with β-blocker, propranolol, suppressed reduction mass....
Abstract Osteoclasts are unique cells that resorb bone, and involved in not only bone remodeling but also pathological loss such as osteoporosis rheumatoid arthritis. The regulation of osteoclasts is based on a number molecules full details these have yet been understood. MicroRNAs produced by Dicer cleavage an emerging regulatory system for cell tissue function. Here, we examine the effects deficiency osteoclastic activity mass vivo. We specifically knocked out crossing flox mice with...
Renin angiotensin system (RAS) regulates circulating blood volume and pressure systemically, whereas RAS also plays a role in the local milieu. Previous vitro studies suggested that may be involved regulation of bone cells. However, it was not known whether molecules are present vivo. In this study, we examined presence components adult effects II type 2 (AT2) receptor blocker on mass. Immunohistochemistry revealed AT2 protein expressed both osteoblasts osteoclasts. addition, renin...
Abstract Mechanosensing is one of the crucial components biological events. In bone, as observed in unloading‐induced osteoporosis bed ridden patients, mechanical stress determines levels bone mass. Many molecules have been suggested to be involved sensing while full pathways for this event has not yet identified. We examined role TRPV4 loss. Hind limb unloading induced osteopenia wild‐type mice. contrast, deficiency suppressed such As underlying mechanism effects, reduction mineral...
Abstract Bone regeneration for the defects in revision surgery of joint replacement is an increasingly important issue. To repair bone defects, cell activation by growth factors using synthetic resorbable scaffold a useful and safe option. We examine efficiency nanogel‐crosslinking hydrogel as novel BMP to stimulate osteoblasts induce formation. Cholesterol‐bearing pullulan (CHPA/Hydrogel) was used deliver BMP. The CHPA pellets were implanted vivo. Single implantation CHPA/hydrogel...
The sympathetic nervous system suppresses bone mass by mechanisms that remain incompletely elucidated. Using cell-based and murine genetics approaches, we show this activity of the requires osteopontin (OPN), a cytokine one major members noncollagenous extracellular matrix proteins bone. In work, found stimulation tone isoproterenol increased level OPN expression in plasma mice lacking (OPN-KO) suppressed isoproterenol-induced loss preventing reduced osteoblastic enhanced osteoclastic...
Abstract Objective Human synovium–derived mesenchymal stem cells (MSCs) can efficiently differentiate into mature chondrocytes. It has been suggested that DNA methylation is one mechanism regulates human chondrogenesis; however, the status of genes related to chondrogenic differentiation not known. The purpose this study was investigate CpG in MSCs during experimental chondrogenesis, with a view toward potential therapeutic use osteoarthritis. Methods were subjected pellet culture for 3...
Parathyroid hormone (PTH), the major calcium-regulating hormone, and norepinephrine (NE), principal neurotransmitter of sympathetic nerves, regulate bone remodeling by activating distinct cell-surface G protein-coupled receptors in osteoblasts: parathyroid type 1 receptor (PTHR) β 2 -adrenergic (β AR), respectively. These activate a common cAMP/PKA signal transduction pathway mediated through stimulatory heterotrimeric protein. Activation AR via nervous system decreases formation increases...
Bone formation is precisely regulated by cell-cell communication in osteoblasts. We have previously demonstrated that genetic deletion of Col6a1 or Col12a1 impairs osteoblast connections and/or mice, resulting bone mass reduction and fragility. Mutations the genes encoding collagen VI cause Ullrich congenital muscular dystrophy (UCMD) Bethlem myopathy (BM), which overlapping phenotypes involving connective tissue muscle. Recent studies identified COL12A1 gene mutations patients with UCMD-...
Mechanical stress to bone plays a crucial role in the maintenance of homeostasis. It causes deformation matrix and generates strain force, which could initiate mechano-transduction pathway. The presence osteopontin (OPN), is one abundant proteins matrix, required for effects mechanical on bone, as we have reported that OPN-null (OPN-/-) mice showed resistance unloading-induced loss. However, cellular mechanisms underlying phenomenon not been completely elucidated. To obtain further insight...
Abstract Recovery of bone loss is one the active research issues in medicine due to need for efficient measures gain. We examined here a novel drug delivery system using nanogel cholesterol‐bearing pullulan (CHP) combination with prostaglandin E 2 (PGE ). PGE or /CHP, vehicle (saline containing 0.06% ethanol and 0.02% Tween 80) CHP were injected on calvariae mice once every day 5 days per week 4 weeks. Low dosage (0.6 µg) alone did not induce new formation this system. In contrast, µg)/CHP...
Regeneration of bone requires the combination appropriate drugs and an delivery system to control cell behavior. However, multiple heal is complicated by availability carriers. The aim this study was explore a new for selective EP4 receptor agonist (EP4A) in with low-dose morphogenetic protein 2 (BMP-2).Combined EP4A BMP-2 carried out nanogel-based scaffold shape disc, repair critical-size circle-shaped defects calvariae that otherwise did not spontaneously.Combination treatment nanogel...
We performed quantitative analysis of synovial fibrosis in the infrapatellar fat pad 26 patients who under went arthroscopically assisted anterior cruciate liga ment reconstructions. Twelve underwent re construction with patellar tendon autografts, and 14 had reconstructions semitendinosus gracilis autografts. Synovial samples were obtained at time reconstruction from 10 second-look arthroscopy all patients. Sections quick-frozen stained either hematoxylin eosin or Fast green Sirius red....
Abstract Tumor malignancy is associated with several features such as proliferation ability and frequency of metastasis. Since tumor metastasis shortens patients' lifetime, establishment therapy for anti‐metastasis very important. Osteopontin (OPN), which abundantly expressed in bone matrix, involved cell adhesion, migration, extracellular matrix (ECM) invasion via interaction its receptor, that is, αvβ3 integrin. OPN believed to be a positive regulator vivo. However, how regulates largely...
Abstract Osteopontin (OPN) is a major non‐collagenous bone matrix protein implicated in the regulation of cell function. Although OPN rich cementum tooth, significance this tissue not understood. Tooth root resorption most frequent complication orthodontic tooth movement (TM). The objective study was to examine pathophysiological role root. For purpose, upper right first molar (M1) OPN‐deficient and wild‐type (WT) mice subjected mechanical force via 10 gf NiTi coil spring while left side...