- Bone Metabolism and Diseases
- Bone health and treatments
- Osteoarthritis Treatment and Mechanisms
- TGF-β signaling in diseases
- NF-κB Signaling Pathways
- FOXO transcription factor regulation
- Bone fractures and treatments
- Connective tissue disorders research
- Bone health and osteoporosis research
- Cell death mechanisms and regulation
- Alkaline Phosphatase Research Studies
- Molecular Biology Techniques and Applications
- Erythrocyte Function and Pathophysiology
- interferon and immune responses
- Protease and Inhibitor Mechanisms
- Trace Elements in Health
- Science, Research, and Medicine
- Proteoglycans and glycosaminoglycans research
- Metabolism and Genetic Disorders
- Reproductive Biology and Fertility
- Biochemical Acid Research Studies
- Parathyroid Disorders and Treatments
- Heat shock proteins research
- Genetic Syndromes and Imprinting
- S100 Proteins and Annexins
Nagasaki University
2011-2025
The strength of bone depends on quantity and quality. Osteocalcin (Ocn) is the most abundant noncollagenous protein in produced by osteoblasts. It has been previously claimed that Ocn inhibits formation also functions as a hormone to regulate insulin secretion pancreas, testosterone synthesis testes, muscle mass. We generated Ocn-deficient (Ocn-/-) mice deleting Bglap Bglap2. Analysis Ocn-/-mice revealed not involved regulation quantity, glucose metabolism, synthesis, or orientation degree...
Runx2 and Sp7 are essential transcription factors for osteoblast differentiation. However, the molecular mechanisms responsible proliferation of progenitors remain unclear. The early onset expression caused limb defects through Fgfr1-3 regulation by Runx2. To investigate physiological role in Fgfr1-3, we compared Sp7-/- Runx2-/- mice. Osteoblast accumulated actively proliferated calvariae mandibles but not mice, number their were dependent on gene dosage background. Fgfr2 Fgfr3, which...
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...
Reduced mechanical stress is a major cause of osteoporosis in the elderly, and osteocyte network, which comprises communication system through processes canaliculi throughout bone, thought to be mechanosensor mechanotransduction system; however, functions osteocytes are still controversial remain clarified. Unexpectedly, we found that overexpression BCL2 osteoblasts eventually caused apoptosis. Osteoblast osteoclast differentiation were unaffected by transgene vitro. However, cortical bone...
RUNX2 and SP7 are essential transcription factors for osteoblast differentiation at an early stage. Although inhibits a late stage, the function of stage is not fully elucidated. Thus, we pursued in differentiation. induced Sp7 expression Runx2−/− calvarial cells. Adenoviral transfer sh-Sp7 into primary osteoblasts reduced Alpl, Col1a1, Bglap2 mineralization, whereas that mineralization transgenic mice under control 2.3 kb Col1a1 promoter showed osteopenia woven-bone like structure cortical...
Abstract Osteoclast differentiation is critically dependent on calcium (Ca2+) signaling. Transient receptor potential vanilloid 4 (TRPV4), mediates Ca2+ influx in the late stage of osteoclast and thereby regulates However, system-modifying effect TRPV4 activity remains to be determined. To elucidate mechanisms underlying activation based differentiation, gain-of-function mutants were generated by amino acid substitutions R616Q V620I introduced into lineage Trpv4 null mice generate...
Runx family proteins, Runx1, Runx2, and Runx3, play important roles in skeletal development. Runx2 is required for osteoblast differentiation chondrocyte maturation, haplodeficiency of RUNX2 causes cleidocranial dysplasia, which characterized by open fontanelles sutures hypoplastic clavicles. Cbfb forms a heterodimer with proteins enhances their DNA-binding capacity. Cbfb-deficient (Cbfb(-/-) ) mice die at midgestation because the lack fetal liver hematopoiesis. We previously reported that...
ABSTRACT Runt-related transcription factor-2 (Runx2) is an essential factor for osteoblast differentiation. However, its functions after the commitment into osteoblasts are controversial and remain to be clarified. We generated enhanced green fluorescent protein (EGFP)-Cre transgenic mice driven by 2.3-kilobase (kb) Col1a1 promoter, Runx2 was deleted in odontoblasts Runx2fl/flCre mice. The sutures fontanelles were more widely opened newborns than Runx2fl/fl newborns. exhibited dwarfism with...
Bcl2 subfamily proteins, including and Bcl-XL, inhibit apoptosis. As osteoblast apoptosis is in part responsible for osteoporosis sex steroid deficiency, glucocorticoid excess, aging, bone loss might be inhibited by the upregulation of Bcl2; however, effects overexpression on differentiation development maintenance have not been fully investigated. To investigate these issues, we established two lines osteoblast-specific BCL2 transgenic mice. In mice, volume was increased at 6 weeks age but...
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
Runx2 (runt related transcription factor 2) is an essential for osteoblast proliferation and differentiation. Uridine diphosphate (UDP)-N-acetylgalactosamine (GalNAc): polypeptide GalNAc-transferase 3 (Galnt3) prevents proteolytic processing of fibroblast growth 23 (Fgf23), which a hormone that regulates the serum level phosphorus. Galnt3 were expressed in osteoblasts osteocytes, Fgf23 expression was restricted to osteocytes bone. Overexpression knock-down upregulated downregulated,...
Runx2 is an essential transcription factor for osteoblast differentiation and chondrocyte maturation. The spaciotemporal expression of regulated by enhancers. We previously identified a 1.3-kb osteoblast-specific enhancer; however, mice with its deletion showed no phenotypes. A 0.8-kb conserved region detected near the enhancer did not exhibit activity in reporter assays, whereas four tandem repeats 452 bp (452×4), containing most 0.8 kb, induced strong cell lines. However, chondrocytes...
Runx2 is an essential transcription factor for osteoblast differentiation and chondrocyte maturation. The spatiotemporal expression of regulated by enhancers. We previously identified a 1.3 kb osteoblast-specific enhancer; however, mice with this deletion showed no phenotypes. A 0.8 conserved region detected near the enhancer did not exhibit activity in reporter assays, whereas four tandem repeats 452 bp (452 × 4) containing most induced strong cell lines. However, chondrocytes enhanced...
Osteoblast apoptosis plays an important role in bone development and maintenance, is part responsible for osteoporosis sex steroid deficiency, glucocorticoid excess, aging. Although Bcl2 subfamily proteins, including Bcl-XL, inhibit apoptosis, the physiological significance of osteoblast differentiation has not been fully elucidated. To investigate this, we examined Bcl2-deficient (Bcl2−/−) mice. In Bcl2−/− mice, bromodeoxyuridine (BrdU)-positive osteoblasts were reduced number, while...
The relationship of lacunocanalicular network structure and mechanoresponse has not been well studied. structures differed in the compression tension sides, regions, genders wild-type femoral cortical bone. overexpression Sp7 osteoblasts resulted thin porous bone with increased osteoclasts apoptotic osteocytes, number canaliculi was half that mice, leading to a markedly impaired network. To investigate response unloading, we performed tail suspension. Unloading reduced trabecular transgenic...
ABSTRACT Cbfb is a cotranscription factor that forms heterodimer with Runx proteins Runx1, Runx2, and Runx3. It required for fetal liver hematopoiesis skeletal development. has two functional isoforms, Cbfb1 Cbfb2, which are formed by alternative splicing. To address the biological functions of these isoforms in development, we examined Cbfb1–/– Cbfb2–/– mouse embryos. Intramembranous endochondral ossification was retarded chondrocyte osteoblast differentiation inhibited embryos but not...
Antxr1/Tem8 is highly expressed in tumor endothelial cells and a receptor for anthrax toxin. Mutation of Antxr1 causes GAPO syndrome, which characterized by growth retardation, alopecia, pseudo-anodontia, optic atrophy. However, the mechanism underlying retardation remains to be clarified. Runx2 essential osteoblast differentiation chondrocyte maturation regulates proliferation through Ihh induction. In search target genes chondrocytes, we found that expression upregulated Runx2. was...
RUNX proteins, such as RUNX2, regulate the proliferation and differentiation of chondrocytes osteoblasts. Haploinsufficiency RUNX2 causes cleidocranial dysplasia, but a detailed analysis Runx2+/- mice has not been reported. Furthermore, CBFB is required for stability DNA binding family proteins. two isoforms, CBFB2 plays major role in skeletal development. The calvaria, femurs, vertebrae ribs Cbfb2-/- were analyzed after birth, compared with those mice. Calvarial development was impaired...