The Experts below are selected from a list of 1653 Experts worldwide ranked by ideXlab platform
Akira Kudo - One of the best experts on this subject based on the ideXlab platform.
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periostin a novel marker of Intramembranous Ossification is expressed in fibrous dysplasia and in c fos overexpressing bone lesions
Human Pathology, 2009Co-Authors: Takeshi Kashima, Takashi Nishiyama, Kazuhiro Shimazu, Masashi Shimazaki, Isao Kii, Agamemnon E Grigoriadis, Masashi Fukayama, Akira KudoAbstract:Summary Fibrous dysplasia is a benign bone disease caused by a mutation in the gene for the stimulatory guanine nucleotide-binding protein Gs α , leading to high cyclic adenosine monophosphate levels. Histologically, fibrous dysplasia is characterized by the production of fibrous tissue accompanied by the deposition of ectopic type I collagen and other bone-associated extracellular matrix proteins, as well as by irregular woven Intramembranous bone onto which type I collagen-containing Sharpey fibers are often attached. Fibrous dysplasia is also characterized by high expression of c-Fos/c-Jun, known targets for cyclic adenosine monophosphate signaling. In this study, we examined the expression of the bone-related extracellular matrix protein, periostin, and its known receptor, integrin α v β 3 (CD51/61), in normal bones as well as in fibrous dysplasia. Immunohistochemistry and in situ hybridization studies revealed that periostin was expressed in the extracellular matrix during Intramembranous but not endochondral Ossification, as well as in the fibrous component of fibrous dysplasia; and all cells adjacent to periostin-positive regions expressed CD51/61. Importantly, periostin was abundantly localized to Sharpey fibers. To investigate the contribution of c-Fos, we examined transgenic mice overexpressing c-fos , which develop sclerotic lesions closely resembling those found in fibrous dysplasia. In all lesions, transformed osteoblasts expressed high levels of periostin, whereas normal osteoblasts did not. Our results show that periostin is a novel marker for Intramembranous Ossification, and is a good candidate as a diagnostic tool and/or a therapeutic target in fibrous dysplasia. Moreover, the Gs α –cyclic adenosine monophosphate–c-Fos pathway might represent one mechanism of periostin up-regulation in fibrous dysplasia, resulting in altered collagen fibrillogenesis characteristic of this disease.
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periostin a novel marker of Intramembranous Ossification is expressed in fibrous dysplasia and in c fos overexpressing bone lesions
Human Pathology, 2009Co-Authors: Takeshi Kashima, Takashi Nishiyama, Kazuhiro Shimazu, Masashi Shimazaki, Isao Kii, Agamemnon E Grigoriadis, Masashi Fukayama, Akira KudoAbstract:Fibrous dysplasia is a benign bone disease caused by a mutation in the gene for the stimulatory guanine nucleotide-binding protein Gs alpha, leading to high cyclic adenosine monophosphate levels. Histologically, fibrous dysplasia is characterized by the production of fibrous tissue accompanied by the deposition of ectopic type I collagen and other bone-associated extracellular matrix proteins, as well as by irregular woven Intramembranous bone onto which type I collagen-containing Sharpey fibers are often attached. Fibrous dysplasia is also characterized by high expression of c-Fos/c-Jun, known targets for cyclic adenosine monophosphate signaling. In this study, we examined the expression of the bone-related extracellular matrix protein, periostin, and its known receptor, integrin alpha v beta 3 (CD51/61), in normal bones as well as in fibrous dysplasia. Immunohistochemistry and in situ hybridization studies revealed that periostin was expressed in the extracellular matrix during Intramembranous but not endochondral Ossification, as well as in the fibrous component of fibrous dysplasia; and all cells adjacent to periostin-positive regions expressed CD51/61. Importantly, periostin was abundantly localized to Sharpey fibers. To investigate the contribution of c-Fos, we examined transgenic mice overexpressing c-fos, which develop sclerotic lesions closely resembling those found in fibrous dysplasia. In all lesions, transformed osteoblasts expressed high levels of periostin, whereas normal osteoblasts did not. Our results show that periostin is a novel marker for Intramembranous Ossification, and is a good candidate as a diagnostic tool and/or a therapeutic target in fibrous dysplasia. Moreover, the Gs alpha-cyclic adenosine monophosphate-c-Fos pathway might represent one mechanism of periostin up-regulation in fibrous dysplasia, resulting in altered collagen fibrillogenesis characteristic of this disease.
Peter I Croucher - One of the best experts on this subject based on the ideXlab platform.
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slc20a2 encoding the phosphate transporter pit2 is an important genetic determinant of bone quality and strength
Journal of Bone and Mineral Research, 2019Co-Authors: Sarah Beckcormier, Christopher J Lelliott, John G Logan, David T Lafont, Laure Merametdjian, Victoria D Leitch, Natalie C Butterfield, Hayley Protheroe, Peter I CroucherAbstract:Osteoporosis is characterized by low bone mineral density (BMD) and fragility fracture and affects over 200 million people worldwide. Bone quality describes the material properties that contribute to strength independently of BMD, and its quantitative analysis is a major priority in osteoporosis research. Tissue mineralization is a fundamental process requiring calcium and phosphate transporters. Here we identify impaired bone quality and strength in Slc20a2-/- mice lacking the phosphate transporter SLC20A2. Juveniles had abnormal endochondral and Intramembranous Ossification, decreased mineral accrual, and short stature. Adults exhibited only small reductions in bone mass and mineralization but a profound impairment of bone strength. Bone quality was severely impaired in Slc20a2-/- mice: yield load (-2.3 SD), maximum load (-1.7 SD), and stiffness (-2.7 SD) were all below values predicted from their bone mineral content as determined in a cohort of 320 wild-type controls. These studies identify Slc20a2 as a physiological regulator of tissue mineralization and highlight its critical role in the determination of bone quality and strength. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
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Slc20a2, encoding the phosphate transporter PiT2, is a novel genetic determinant of bone quality and strength
'Wiley', 2019Co-Authors: Beck-cormier S, Christopher J Lelliott, Peter I Croucher, Jg Logan, Dt Lafont, Vd Leitch, Nc Butterfield, Hj Protheroe, Pa Baldock, Gaultier-lintia AAbstract:Osteoporosis is characterized by low bone mineral density (BMD) and fragility fracture and affects over 200 million people worldwide. Bone quality describes the material properties that contribute to strength independently of BMD, and its quantitative analysis is a major priority in osteoporosis research. Tissue mineralization is a fundamental process requiring calcium and phosphate transporters. Here we identify impaired bone quality and strength in Slc20a2–/– mice lacking the phosphate transporter SLC20A2. Juveniles had abnormal endochondral and Intramembranous Ossification, decreased mineral accrual, and short stature. Adults exhibited only small reductions in bone mass and mineralization but a profound impairment of bone strength. Bone quality was severely impaired in Slc20a2–/– mice: yield load (–2.3 SD), maximum load (–1.7 SD), and stiffness (–2.7 SD) were all below values predicted from their bone mineral content as determined in a cohort of 320 wild‐type controls. These studies identify Slc20a2 as a physiological regulator of tissue mineralization and highlight its critical role in the determination of bone quality and strength
Takeshi Kashima - One of the best experts on this subject based on the ideXlab platform.
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periostin a novel marker of Intramembranous Ossification is expressed in fibrous dysplasia and in c fos overexpressing bone lesions
Human Pathology, 2009Co-Authors: Takeshi Kashima, Takashi Nishiyama, Kazuhiro Shimazu, Masashi Shimazaki, Isao Kii, Agamemnon E Grigoriadis, Masashi Fukayama, Akira KudoAbstract:Summary Fibrous dysplasia is a benign bone disease caused by a mutation in the gene for the stimulatory guanine nucleotide-binding protein Gs α , leading to high cyclic adenosine monophosphate levels. Histologically, fibrous dysplasia is characterized by the production of fibrous tissue accompanied by the deposition of ectopic type I collagen and other bone-associated extracellular matrix proteins, as well as by irregular woven Intramembranous bone onto which type I collagen-containing Sharpey fibers are often attached. Fibrous dysplasia is also characterized by high expression of c-Fos/c-Jun, known targets for cyclic adenosine monophosphate signaling. In this study, we examined the expression of the bone-related extracellular matrix protein, periostin, and its known receptor, integrin α v β 3 (CD51/61), in normal bones as well as in fibrous dysplasia. Immunohistochemistry and in situ hybridization studies revealed that periostin was expressed in the extracellular matrix during Intramembranous but not endochondral Ossification, as well as in the fibrous component of fibrous dysplasia; and all cells adjacent to periostin-positive regions expressed CD51/61. Importantly, periostin was abundantly localized to Sharpey fibers. To investigate the contribution of c-Fos, we examined transgenic mice overexpressing c-fos , which develop sclerotic lesions closely resembling those found in fibrous dysplasia. In all lesions, transformed osteoblasts expressed high levels of periostin, whereas normal osteoblasts did not. Our results show that periostin is a novel marker for Intramembranous Ossification, and is a good candidate as a diagnostic tool and/or a therapeutic target in fibrous dysplasia. Moreover, the Gs α –cyclic adenosine monophosphate–c-Fos pathway might represent one mechanism of periostin up-regulation in fibrous dysplasia, resulting in altered collagen fibrillogenesis characteristic of this disease.
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periostin a novel marker of Intramembranous Ossification is expressed in fibrous dysplasia and in c fos overexpressing bone lesions
Human Pathology, 2009Co-Authors: Takeshi Kashima, Takashi Nishiyama, Kazuhiro Shimazu, Masashi Shimazaki, Isao Kii, Agamemnon E Grigoriadis, Masashi Fukayama, Akira KudoAbstract:Fibrous dysplasia is a benign bone disease caused by a mutation in the gene for the stimulatory guanine nucleotide-binding protein Gs alpha, leading to high cyclic adenosine monophosphate levels. Histologically, fibrous dysplasia is characterized by the production of fibrous tissue accompanied by the deposition of ectopic type I collagen and other bone-associated extracellular matrix proteins, as well as by irregular woven Intramembranous bone onto which type I collagen-containing Sharpey fibers are often attached. Fibrous dysplasia is also characterized by high expression of c-Fos/c-Jun, known targets for cyclic adenosine monophosphate signaling. In this study, we examined the expression of the bone-related extracellular matrix protein, periostin, and its known receptor, integrin alpha v beta 3 (CD51/61), in normal bones as well as in fibrous dysplasia. Immunohistochemistry and in situ hybridization studies revealed that periostin was expressed in the extracellular matrix during Intramembranous but not endochondral Ossification, as well as in the fibrous component of fibrous dysplasia; and all cells adjacent to periostin-positive regions expressed CD51/61. Importantly, periostin was abundantly localized to Sharpey fibers. To investigate the contribution of c-Fos, we examined transgenic mice overexpressing c-fos, which develop sclerotic lesions closely resembling those found in fibrous dysplasia. In all lesions, transformed osteoblasts expressed high levels of periostin, whereas normal osteoblasts did not. Our results show that periostin is a novel marker for Intramembranous Ossification, and is a good candidate as a diagnostic tool and/or a therapeutic target in fibrous dysplasia. Moreover, the Gs alpha-cyclic adenosine monophosphate-c-Fos pathway might represent one mechanism of periostin up-regulation in fibrous dysplasia, resulting in altered collagen fibrillogenesis characteristic of this disease.
K Kumaki - One of the best experts on this subject based on the ideXlab platform.
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1 25 dihydroxyvitamin d3 and 22 oxa 1 25 dihydroxyvitamin d3 in vivo nuclear receptor binding in developing bone during endochondral and Intramembranous Ossification
Histochemistry and Cell Biology, 1994Co-Authors: Walter E Stumpf, N Koike, Naohiko Hayakawa, K Tokuda, K Nishimiya, Y Tsuchiya, J Hirate, A Okazaki, K KumakiAbstract:Target cells for 3H-labeled 1α, 25(OH)2 vitamin D3 [1,25(OH)2D3, vitamin D] and its analog 3H-labeled 22-oxa-1α, 25(OH)2 vitamin D3 (OCT) have been identified during endochondral and Intramembranous Ossification in developing, undecalcified, unembedded bone, using thaw-mount autoradiography. Two-day-old neonatal rats were injected with [3H]1,25(OH)2D3 or [3H]OCT; after 2 h leg, spine, and head were frozen and sectioned. In the epiphyseal-metaphyseal region specific nuclear concentrations of [3H]1,25(OH)2D3 and [3H]OCT were observed in identical cell populations, being low in cells of the articular and resting zone, intermediate in the proliferating zone, and highest in hypertrophic chondrocytes and in osteoblasts and precursor cells. In the primary spongiosa intertrabecular spaces there were a large number of cells with nuclear labeling — probably osteoblasts and precursor cells. In contrast, in the secondary spongiosa intertrabecular spaces, apparent blood-forming cells were mostly unlabeled. Osteoblasts along bone spicules and compact bone in long bones, vertebrae, and head also showed strong nuclear labeling, as did cells of the periosteum. These data suggest that 1,25(OH)2D3 and OCT regulate development, differentiation, and activities of chondrocytes and osteoblasts, including differentiation of resting chondrocytes into proliferating and hypertrophic chondrocytes that involve “chondroclastic” enlargement of lacunae and “trans-differentiation” of surviving hypertrophic chondrocytes; differentiation of stroma cells into osteoblasts; and in periosteum and other regions of Intramembranous Ossification differentiation of precursor cells and osteoblasts. Nuclear receptor binding and their selective and hierarchical distribution during cell differentiation appear to correspond to multiple genomic effects toward growth, regeneration and repair. The findings indicate a physiological significance and therapeutic potential of 1,25(OH)2D3 and in particular of its less hypercalcemic analog OCT.
Bjorn Olsen - One of the best experts on this subject based on the ideXlab platform.
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soluble vegfr1 reverses bmp2 inhibition of Intramembranous Ossification during healing of cortical bone defects
Journal of Orthopaedic Research, 2017Co-Authors: Tatiana Y Besschetnova, Bjorn OlsenAbstract:BMP2 is widely used for promotion of bone repair and regeneration. However, bone formation induced by BMP2 is quite variable. Bone forming progenitor cells in different locations appear to respond to BMP2 in different ways, and repair outcomes can vary as a consequence of modulating effects by other factors. In this study, we have examined the effects of VEGF on BMP2-induced repair of a cortical bone defect, a 1 mm diameter drill hole, in the proximal tibia of mice. Treatment of the defect with either a bolus of PBS or soluble VEGFR1 (sVEGFR1), a decoy receptor for VEGF, had the same effects on bone formation via Intramembranous Ossification in the defect and cartilage formation and injured periosteum, during the healing process. In contrast, treatment with BMP2 inhibited Intramembranous bone formation in the defect while it promoted cartilage and endochondral bone formation in the injured periosteum compared with mice treated with PBS or sVEGFR1. The inhibitory effect of BMP2 on bone formation was unlikely due to increased osteoclast activity and decreased invasion of blood vessels in the defect. Most importantly, co-delivery of BMP2 and sVEGFR1 reversed the inhibition of Intramembranous bone formation by BMP2. Furthermore, the decreased accumulation of collagen and production of bone matrix proteins in the defect of groups with BMP2 treatment could also be prevented by co-delivery of BMP2 and sVEGFR1. Our data indicate that introducing a VEGF-binding protein, such as sVEGFR1, to reduce levels of extracellular VEGF, may enhance the effects of BMP2 on Intramembranous bone formation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1461-1469, 2017.
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heritable diseases of the skeleton part i molecular insights into skeletal development transcription factors and signaling pathways
The FASEB Journal, 1997Co-Authors: Stefan Mundlos, Bjorn OlsenAbstract:The recent identification of the genetic basis of hereditary skeletal disorders is providing important insights into the intricate processes of skeletal formation, growth, and homeostasis. These processes include patterning events during condensation and differentiation of mesenchymal cells to form cartilage precursors of the future bones, the replacement of cartilage by bones through endochondral Ossification, the growth of long bones through proliferation and differentiation of chondrocytes in growth plates, and bone formation through differentiation of osteoblasts from mesenchymal cells in areas of Intramembranous Ossification. Defects in any of these processes can give rise to skeletal abnormalities. Mutations in transcription factors such as HOX and PAX and members of the transforming growth factor-beta superfamily cause disorders associated with abnormal mesenchymal condensation, whereas defects in the transcription factor SOX-9 lead to abnormalities in chondrocyte differentiation. Abnormal growth plate function, resulting in dwarfism, is the consequence of mutations in receptors for fibroblast growth factors and parathyroid hormone-related peptide. Premature closure of cranial sutures in Intramembranous Ossification is a feature of syndromes due to mutations in fibroblast growth factor receptors.