A5016126494- Heterotopic Ossification and Related Conditions
- TGF-β signaling in diseases
- Parathyroid Disorders and Treatments
- Bone Metabolism and Diseases
- Medical Imaging and Pathology Studies
- Bone health and treatments
- Bone Tissue Engineering Materials
- Genetic Syndromes and Imprinting
- Orthopaedic implants and arthroplasty
- Connective tissue disorders research
- MicroRNA in disease regulation
- Bone and Dental Protein Studies
- Muscle Physiology and Disorders
- Periodontal Regeneration and Treatments
- Alkaline Phosphatase Research Studies
- dental development and anomalies
- Circular RNAs in diseases
- NF-κB Signaling Pathways
- Cancer-related gene regulation
- RNA Research and Splicing
- Bone Tumor Diagnosis and Treatments
- Medical and Biological Sciences
- Cancer-related molecular mechanisms research
- Bone fractures and treatments
- Wnt/β-catenin signaling in development and cancer
Saitama Medical University
2015-2024
Ministry of Health Labour and Welfare
2008-2011
Center for Genomic Science
2006
American Association of Endodontists
2005
University of Michigan
2005
Showa University
1990-2003
Massachusetts General Hospital
2002
Bayer (Netherlands)
1999
The University of Texas MD Anderson Cancer Center
1998
Tokyo Women's Medical University
1994
The implantation of bone morphogenetic protein (BMP) into muscular tissues induces ectopic formation at the site implantation. To investigate mechanism underlying this process, we examined whether recombinant protein-2 (BMP-2) converts differentiation pathway clonal myoblastic cell line, C2C12, that osteoblast lineage. Incubating cells with 300 ng/ml BMP-2 for 6 d almost completely inhibited multinucleated myotubes expressing troponin T and myosin heavy chain, induced appearance numerous...
The in vitro effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on osteogenic and myogenic differentiation was examined two clonal cell lines rat osteoblast-like cells at different stages, ROB-C26 (C26) ROB-C20 (C20). C26 is a potential osteoblast precursor line that also capable differentiating into muscle adipocytes; the C20 more differentiated osteoblastic line. Proliferation stimulated by rhBMP-2 cells, but inhibited cells. greatly increased alkaline phosphate (ALP)...
In developing murine growth plates, chondrocytes near the articular surface (periarticular chondrocytes) proliferate, differentiate into flat column-forming proliferating cells (columnar chondrocytes), stop dividing and finally hypertrophic cells. Indian hedgehog (Ihh), which is predominantly expressed in prehypertrophic cells, stimulates expression of parathyroid hormone (PTH)-related peptide (PTHrP) negatively regulates terminal chondrocyte differentiation through PTH/PTHrP receptor (PPR)....
Although bone morphogenetic proteins (BMPs) are clinically useful for regeneration, large amounts required to induce new formation in monkeys and humans. We found recently that heparin stimulates BMP activity vitro (Takada, T., Katagiri, Ifuku, M., Morimura, N., Kobayashi, Hasegawa, K., Ogamo, A., Kamijo, R. (2003) J. Biol. Chem. 278, 43229-43235). In the present study, we examined whether enhances induced by BMPs vivo attempted determine molecular mechanism which using C2C12 myoblasts....
Bone morphogenetic proteins (BMPs), which have been shown to be heparin-binding proteins, induce osteoblast differentiation in mesenchymal cells. In the present study, we examined effects of heparin on BMP activities C2C12 myoblasts. Heparin dose dependently enhanced induced by not only homodimers BMP-2 or BMP-4 but also heterodimers BMP-2/6 BMP-2/7. However, constitutively active BMPR-IA, a functional type I receptor, was affected heparin. Heparan sulfate and dextran activity, although...
Bone is a major storage site for TGFbeta superfamily members, including and bone morphogenetic proteins. It believed that these cytokines are released from during resorption. Recent studies have shown both RANKL macrophage colony-stimulating factor two essential factors produced by osteoblasts inducing osteoclast differentiation. In the present study we examined effects of protein-2 on differentiation survival supported and/or factor. Mouse marrow-derived macrophages differentiated into...
Abstract Background: Bone morphogenetic protein‐2 (BMP‐2) stimulates osteoblast differentiation, but inhibits myogenic differentiation in C2C12 myoblasts. BMP‐2 induces transcription of Id1 , an inhibitor for myogenesis, within 1 h the cells. To examine molecular mechanism action BMP‐2, we analysed a BMP‐2‐responsive element (BRE) 5′ flanking region human gene. Results: A GC‐rich between −985 bp and −957 gene was identified as BRE. The BRE containing promoter activity stimulated by or...
Patients with classic fibrodysplasia ossificans progressiva, a disorder characterized by extensive extraskeletal endochondral bone formation, share recurrent mutation (R206H) within the glycine/serine-rich domain of ACVR1/ALK2, morphogenetic protein type I receptor. Through series in vitro assays using several mammalian cell lines and chick limb bud micromass cultures, we determined that mutant R206H ACVR1 activated BMP signaling absence ligand mediated BMP-independent chondrogenesis was...
Although microRNAs (miRNAs) are involved in many biological processes, the mechanisms whereby miRNAs regulate osteoblastic differentiation poorly understood. Here, we found that BMP‐4‐induced of bone marrow‐derived ST2 stromal cells was promoted and repressed after transfection sense antisense miR‐210, respectively. A reporter assay demonstrated activin receptor type 1B ( AcvR1b ) gene a target for miR‐210. Furthermore, inhibition transforming growth factor‐β (TGF‐β)/activin signaling with...
Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by congenital malformation of the great toes and progressive heterotopic bone formation in muscle tissue. Recently, mutation involving single amino acid substitution morphogenetic protein (BMP) type I receptor, ALK2, was identified patients with FOP. We report here that identical mutation, R206H, observed 19 Japanese sporadic This mutant ALK2(R206H), activates BMP signaling without ligand binding....
MicroRNAs (miRNAs) play critical roles in a variety of biological processes diverse organisms, including mammals. In the mouse skeletal system, global reduction miRNAs chondrocytes causes lethal dysplasia. However, little is known about physiological individual chondrocytes. The miRNA-encoding gene, Mir140, evolutionarily conserved among vertebrates and abundantly almost exclusively expressed this paper, we show that loss Mir140 mice growth defects endochondral bones, resulting dwarfism...
Smad1, Smad5 and Smad9 (also known as Smad8) are activated by phosphorylation bone morphogenetic protein (BMP)-bound type I receptor kinases. We examined the role of creating constitutively active forms (SmadDVD). Transcriptional activity Smad9DVD was lower than that Smad1DVD or Smad5DVD, even though all three SmadDVDs associated with Smad4 bound to target DNA. The linker region sufficient reduce transcriptional activity. expression increased activation BMP signaling, similar inhibitory...
Although accumulated evidence has shown the bone anabolic effects of morphogenetic proteins (BMPs) that were exogenously applied in vitro and vivo, roles endogenous BMPs during formation remain to be clarified. This study initially investigated expression patterns mouse long found BMP2 BMP6 main subtypes expressed hypertrophic chondrocytes induce endochondral formation. We then examined involvement combination these vivo by generating compound-deficient mice (Bmp2+/-;Bmp6-/-). Under...