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Shin-ichi Hayashi - One of the best experts on this subject based on the ideXlab platform.
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sequential requirements for scl tal 1 gata 2 macrophage colony stimulating Factor and Osteoclast Differentiation Factor osteoprotegerin ligand in Osteoclast development
Experimental Hematology, 2000Co-Authors: Toshiyuki Yamane, Takahiro Kunisada, Hidetoshi Yamazaki, Toru Nakano, Stuart H. Orkin, Shin-ichi HayashiAbstract:Abstract Objective Osteoclasts are of hematopoietic origin. The mechanism by which hematopoietic stem cells are specified to the Osteoclast lineage is unclear. To understand the process of generation and Differentiation of this lineage of cells, we performed in vitro studies on the Differentiation of embryonic stem cells. Materials and Methods We examined the potential of mutant embryonic stem cell lines harboring targeted deletions of the GATA-1 , FOG , SCL/tal-1 , or GATA-2 genes to differentiate into Osteoclasts and determined when these molecules function in Osteoclast development. Results The lack of GATA-1 or FOG did not affect Osteoclastogenesis. In contrast, SCL/tal-1 -null embryonic stem cells generated no Osteoclasts. In the case of the loss of GATA-2, a small number of Osteoclasts were generated. GATA-2 -null Osteoclasts were morphologically normal and the terminal maturation was not disturbed, but a defect was observed in the generation of Osteoclast progenitors. Experiments using specific inhibitors that block the signaling through macrophage colony-stimulating Factor and Osteoclast Differentiation Factor/osteoprotegerin ligand suggested that GATA-2 seems to act earlier in Osteoclastogenesis than these cytokines. Interestingly, macrophage colony-forming units were not severely reduced by the loss of GATA-2 compared to Osteoclast progenitors . Conclusion These results indicate that osteocalsts need SCL/tal-1 at an early point in development, and that GATA-2 is required for generation of Osteoclast progenitors but not for the later stages when macrophage colony-stimulating Factor and Osteoclast Differentiation Factor/osteoprotegerin ligand are needed. We also demonstrated that Osteoclast progenitors behave as a different population than macrophage colony-forming units.
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Sequential requirements for SCL/tal-1, GATA-2, macrophage colony-stimulating Factor, and Osteoclast Differentiation Factor/osteoprotegerin ligand in Osteoclast development.
Experimental hematology, 2000Co-Authors: Toshiyuki Yamane, Takahiro Kunisada, Hidetoshi Yamazaki, Toru Nakano, Stuart H. Orkin, Shin-ichi HayashiAbstract:Abstract Objective Osteoclasts are of hematopoietic origin. The mechanism by which hematopoietic stem cells are specified to the Osteoclast lineage is unclear. To understand the process of generation and Differentiation of this lineage of cells, we performed in vitro studies on the Differentiation of embryonic stem cells. Materials and Methods We examined the potential of mutant embryonic stem cell lines harboring targeted deletions of the GATA-1 , FOG , SCL/tal-1 , or GATA-2 genes to differentiate into Osteoclasts and determined when these molecules function in Osteoclast development. Results The lack of GATA-1 or FOG did not affect Osteoclastogenesis. In contrast, SCL/tal-1 -null embryonic stem cells generated no Osteoclasts. In the case of the loss of GATA-2, a small number of Osteoclasts were generated. GATA-2 -null Osteoclasts were morphologically normal and the terminal maturation was not disturbed, but a defect was observed in the generation of Osteoclast progenitors. Experiments using specific inhibitors that block the signaling through macrophage colony-stimulating Factor and Osteoclast Differentiation Factor/osteoprotegerin ligand suggested that GATA-2 seems to act earlier in Osteoclastogenesis than these cytokines. Interestingly, macrophage colony-forming units were not severely reduced by the loss of GATA-2 compared to Osteoclast progenitors . Conclusion These results indicate that osteocalsts need SCL/tal-1 at an early point in development, and that GATA-2 is required for generation of Osteoclast progenitors but not for the later stages when macrophage colony-stimulating Factor and Osteoclast Differentiation Factor/osteoprotegerin ligand are needed. We also demonstrated that Osteoclast progenitors behave as a different population than macrophage colony-forming units.
Sakae Tanaka - One of the best experts on this subject based on the ideXlab platform.
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RANKL as a therapeutic target of rheumatoid arthritis
Journal of Bone and Mineral Metabolism, 2020Co-Authors: Sakae Tanaka, Yoshiya TanakaAbstract:Rheumatoid arthritis (RA) is an inflammatory disorder characterized by progressive joint destruction. Recent studies have demonstrated that Osteoclasts are responsible for bone destruction in RA. Receptor activator of nuclear Factor kappa B ligand (RANKL), an Osteoclast Differentiation Factor, belongs to the tumor necrosis Factor superfamily and plays a critical role in Osteoclast Differentiation. RANKL is highly expressed in the synovial tissues in patients with RA and is involved in Osteoclast development and thus bone destruction in RA. Denosumab, a specific antibody to human RANKL, efficiently suppressed the progression of bone destruction in patients with RA in a randomized controlled study and is considered a putative therapeutic option for RA.
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RANKL: A therapeutic target for bone destruction in rheumatoid arthritis.
Modern rheumatology, 2017Co-Authors: Sakae Tanaka, Yoshiya Tanaka, Naoki Ishiguro, Hisashi Yamanaka, Tsutomu TakeuchiAbstract:Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressive joint destruction. Recent studies have indicated the critical involvement of Osteoclasts in bone destruction in RA. The Osteoclast Differentiation Factor receptor activator of NF-κB ligand (RANKL), which belongs to the tumor necrosis Factor superfamily, plays a critical role in Osteoclast Differentiation and bone destruction in RA. Denosumab, an antibody against human RANKL, efficiently suppressed the progression of bone erosion in RA patients in randomized controlled studies, and is considered as a putative therapeutic option for preventing bone destruction in RA.
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Intracellular signal transduction pathways: good therapeutic targets for joint destruction in rheumatoid arthritis.
Modern rheumatology, 2005Co-Authors: Sakae TanakaAbstract:Preventing joint destruction is one of the most challenging issues in treating patients with rheumatoid arthritis (RA), and I propose that intracellular signaling pathways in Osteoclasts and synovial fibroblastic cells (SFCs) can be good therapeutic targets. Osteoclasts are primarily involved in the bone destruction in RA joints, and SFCs support Osteoclast Differentiation and activation by producing various proinflammatory cytokines including receptor activator of NF-κB ligand (RANKL), the Osteoclast Differentiation Factor belonging to the tumor necrosis Factor-α superfamily. Suppressing c-Src pathways by adenovirus vector-mediated C-terminal Src family kinase (Csk) gene or Ras/extracellular-regulating kinase (ERK) pathways by introducing dominant negative Ras (RasDN) adenovirus reduced Osteoclastic bone resorption as well as the abnormal proliferation and interleukin-6 production of SFCs, and the local injection of these viruses ameliorated the joint destruction in adjuvant arthritis rats. Moreover, chondrogenic Differentiation of SFCs could be induced by stimulating activin receptor-like kinase 3 pathways.
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involvement of receptor activator of nuclear Factor κb ligand Osteoclast Differentiation Factor in Osteoclastogenesis from synoviocytes in rheumatoid arthritis
Arthritis & Rheumatism, 2000Co-Authors: Hiroshi Takayanagi, Hideharu Iizuka, Takuo Juji, Aiichiro Yamamoto, Yasuko Koshihara, Takumi Nakagawa, Tsuyoshi Miyazaki, K. Nakamura, Sakae TanakaAbstract:Objective To clarify the mechanism by which Osteoclasts are formed in culture of rheumatoid synoviocytes by exploring the involvement of receptor activator of nuclear Factor κB ligand (RANKL)/Osteoclast Differentiation Factor (ODF). Methods Osteoclast formation was evaluated in cocultures of rheumatoid synovial fibroblasts and peripheral blood mononuclear cells (PBMC) in the presence of macrophage colony stimulating Factor and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) utilizing separating membrane filters. RANKL/ODF expression was examined by Northern blotting in synovial tissues from 5 rheumatoid arthritis (RA) patients and tissues from patients with giant cell tumor (GCT), osteosarcoma (OS), and osteoarthritis (OA). RANKL/ODF expression and the ability of synovial fibroblasts to support Osteoclastogenesis were investigated in coculture with PBMC in the presence or absence of 1,25(OH)2D3, and soluble RANKL/ODF and osteoprotegerin (OPG)/Osteoclastogenesis inhibitory Factor (OCIF) were measured by enzyme-linked immunosorbent assay. The effects of OPG/OCIF on the Osteoclastogenesis in the primary culture of rheumatoid synoviocytes and the coculture system were determined. Results Synovial fibroblasts did not induce Osteoclastogenesis when separately cocultured with PBMC. Northern blotting revealed that RANKL/ODF was highly expressed in all tissues from RA and GCT patients, but not from OA or OS patients. Cultured rheumatoid synovial fibroblasts efficiently induced Osteoclastogenesis in the presence of 1,25(OH)2D3, which was accompanied by up-regulated expression of RANKL/ODF and decreased production of OPG/OCIF. Osteoclastogenesis from synoviocytes was dose-dependently inhibited by OPG/OCIF. Conclusion RANKL/ODF expressed on synovial fibroblasts is involved in rheumatoid bone destruction by inducing Osteoclastogenesis and would therefore be a good therapeutic target.
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Involvement of receptor activator of nuclear Factor κB ligand/Osteoclast Differentiation Factor in Osteoclastogenesis from synoviocytes in rheumatoid arthritis
Arthritis and rheumatism, 2000Co-Authors: Hiroshi Takayanagi, Hideharu Iizuka, Takuo Juji, Aiichiro Yamamoto, Yasuko Koshihara, Takumi Nakagawa, Tsuyoshi Miyazaki, K. Nakamura, Hiromi Oda, Sakae TanakaAbstract:Objective To clarify the mechanism by which Osteoclasts are formed in culture of rheumatoid synoviocytes by exploring the involvement of receptor activator of nuclear Factor κB ligand (RANKL)/Osteoclast Differentiation Factor (ODF). Methods Osteoclast formation was evaluated in cocultures of rheumatoid synovial fibroblasts and peripheral blood mononuclear cells (PBMC) in the presence of macrophage colony stimulating Factor and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) utilizing separating membrane filters. RANKL/ODF expression was examined by Northern blotting in synovial tissues from 5 rheumatoid arthritis (RA) patients and tissues from patients with giant cell tumor (GCT), osteosarcoma (OS), and osteoarthritis (OA). RANKL/ODF expression and the ability of synovial fibroblasts to support Osteoclastogenesis were investigated in coculture with PBMC in the presence or absence of 1,25(OH)2D3, and soluble RANKL/ODF and osteoprotegerin (OPG)/Osteoclastogenesis inhibitory Factor (OCIF) were measured by enzyme-linked immunosorbent assay. The effects of OPG/OCIF on the Osteoclastogenesis in the primary culture of rheumatoid synoviocytes and the coculture system were determined. Results Synovial fibroblasts did not induce Osteoclastogenesis when separately cocultured with PBMC. Northern blotting revealed that RANKL/ODF was highly expressed in all tissues from RA and GCT patients, but not from OA or OS patients. Cultured rheumatoid synovial fibroblasts efficiently induced Osteoclastogenesis in the presence of 1,25(OH)2D3, which was accompanied by up-regulated expression of RANKL/ODF and decreased production of OPG/OCIF. Osteoclastogenesis from synoviocytes was dose-dependently inhibited by OPG/OCIF. Conclusion RANKL/ODF expressed on synovial fibroblasts is involved in rheumatoid bone destruction by inducing Osteoclastogenesis and would therefore be a good therapeutic target.
Hisataka Yasuda - One of the best experts on this subject based on the ideXlab platform.
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Animal models for bone and joint disease. RANKL-injected bone loss model
Clinical calcium, 2011Co-Authors: Hisataka YasudaAbstract:Discovery of the Osteoclast Differentiation Factor RANKL (receptor activator of NF-κB ligand) has opened a new era in the understanding of mechanisms in Osteoclast Differentiation over the last decade. The discovery results in the development of a fully human anti-RANKL neutralizing monoclonal antibody (called denosumab) and denosumab has been approved for the treatment of osteoporosis in Europe and the US. Here I review a novel rapid bone loss model with GST (glutathione-S-transferase) -RANKL. Pharmacologic studies of candidates for the treatment of osteoporosis with this model can be done in short periods such as 3 days and a couple of weeks although it took several months in the conventional methods with ovariectomized (OVX) -rats. This model also is useful for the rapid analyses in the functions of Osteoclasts in vivo . I am expecting the RANKL-induced bone loss model to be the gold standard in the animal osteoporosis model as well as OVX-rats in the near future.
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OPG, anti-rANKL antibody
Nihon rinsho. Japanese journal of clinical medicine, 2005Co-Authors: Hisataka YasudaAbstract:: Identification of RANKL/ODF (receptor activator of NF-kappaB ligand/Osteoclast Differentiation Factor), RANK(receptor activator of NF-kappaB) and OPG/OCIF(osteoprotegerin/ Osteoclastogenesis inhibitory Factor) revealed the mechanisms regulating Osteoclast Differentiation and function. RANKL-RANK signaling is essential for the physiological Osteoclast development and plays a major role in the pathological bone destruction. OPG and anti-RANKL antibody act as a specific inhibitor of RANKL and are useful and applicable to osteoporosis and rheumatoid arthritis.
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OPG, a possible candidate for the treatment of rheumatoid arthritis
Clinical calcium, 2003Co-Authors: Hisataka YasudaAbstract:Osteoprotegerin (OPG) is an Osteoclastogenesis inhibitory Factor that we have cloned, and is a decoy receptor that inhibits the binding of an Osteoclast Differentiation Factor, RANKL and its receptor RANK. Pharmacological and developmental approaches have demonstrated that OPG inhibits Osteoclastogenesis and bone resorption in vivo. OPG may be useful for and applicable to the treatment of bone destruction in rheumatoid arthritis.
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Osteoprotegerin (OPG/OCIF) inhibits bone destruction in rheumatoid arthritis models
Clinical calcium, 2001Co-Authors: Hisataka YasudaAbstract:Recent discovery of Factors involved in bone destruction in Rheumatoid Arthritis (RA) identified its molecular mechanism. Osteoclast Differentiation Factor (ODF, also called receptor activator of NF-kappaB ligand (RANKL) ) that controls Osteoclast Differentiation and function has a major role in the bone destruction among them. Osteoclastogenesis inhibitory Factor (OCIF, also called osteoprotegerin (OPG) ) that is a decoy receptor for ODF/RANKL is a specific inhibitor of bone destruction. OPG/OCIF may be useful for and applicable to the treatment of bone destruction in RA.
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osteoprotegerin produced by osteoblasts is an important regulator in Osteoclast development and function
Endocrinology, 2000Co-Authors: Nobuyuki Udagawa, Hisataka Yasuda, Atsuko Mizuno, Kanami Itoh, Yutaka Ueno, Toshimasa Shinki, Matthew T Gillespie, John T Martin, Naoyuki Takahashi, Kanji HigashioAbstract:Osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear Factor-κB ligand (RANKL)/Osteoclast Differentiation Factor, inhibits both Differentiation and function of Osteoclasts. We previously reported that OPG-deficient mice exhibited severe osteoporosis caused by enhanced Osteoclastic bone resorption. In the present study, potential roles of OPG in Osteoclast Differentiation were examined using a mouse coculture system of calvarial osteoblasts and bone marrow cells prepared from OPG-deficient mice. In the absence of bone-resorbing Factors, no Osteoclasts were formed in cocultures of wild-type (+/+) or heterozygous (+/−) mouse-derived osteoblasts with bone marrow cells prepared from homozygous (−/−) mice. In contrast, homozygous (−/−) mouse-derived osteoblasts strongly supported Osteoclast formation in the cocultures with homozygous (−/−) bone marrow cells, even in the absence of bone-resorbing Factors. Addition of OPG to the cocultures with osteoblasts and bone marrow cells derived...
Toshiyuki Yamane - One of the best experts on this subject based on the ideXlab platform.
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sequential requirements for scl tal 1 gata 2 macrophage colony stimulating Factor and Osteoclast Differentiation Factor osteoprotegerin ligand in Osteoclast development
Experimental Hematology, 2000Co-Authors: Toshiyuki Yamane, Takahiro Kunisada, Hidetoshi Yamazaki, Toru Nakano, Stuart H. Orkin, Shin-ichi HayashiAbstract:Abstract Objective Osteoclasts are of hematopoietic origin. The mechanism by which hematopoietic stem cells are specified to the Osteoclast lineage is unclear. To understand the process of generation and Differentiation of this lineage of cells, we performed in vitro studies on the Differentiation of embryonic stem cells. Materials and Methods We examined the potential of mutant embryonic stem cell lines harboring targeted deletions of the GATA-1 , FOG , SCL/tal-1 , or GATA-2 genes to differentiate into Osteoclasts and determined when these molecules function in Osteoclast development. Results The lack of GATA-1 or FOG did not affect Osteoclastogenesis. In contrast, SCL/tal-1 -null embryonic stem cells generated no Osteoclasts. In the case of the loss of GATA-2, a small number of Osteoclasts were generated. GATA-2 -null Osteoclasts were morphologically normal and the terminal maturation was not disturbed, but a defect was observed in the generation of Osteoclast progenitors. Experiments using specific inhibitors that block the signaling through macrophage colony-stimulating Factor and Osteoclast Differentiation Factor/osteoprotegerin ligand suggested that GATA-2 seems to act earlier in Osteoclastogenesis than these cytokines. Interestingly, macrophage colony-forming units were not severely reduced by the loss of GATA-2 compared to Osteoclast progenitors . Conclusion These results indicate that osteocalsts need SCL/tal-1 at an early point in development, and that GATA-2 is required for generation of Osteoclast progenitors but not for the later stages when macrophage colony-stimulating Factor and Osteoclast Differentiation Factor/osteoprotegerin ligand are needed. We also demonstrated that Osteoclast progenitors behave as a different population than macrophage colony-forming units.
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Sequential requirements for SCL/tal-1, GATA-2, macrophage colony-stimulating Factor, and Osteoclast Differentiation Factor/osteoprotegerin ligand in Osteoclast development.
Experimental hematology, 2000Co-Authors: Toshiyuki Yamane, Takahiro Kunisada, Hidetoshi Yamazaki, Toru Nakano, Stuart H. Orkin, Shin-ichi HayashiAbstract:Abstract Objective Osteoclasts are of hematopoietic origin. The mechanism by which hematopoietic stem cells are specified to the Osteoclast lineage is unclear. To understand the process of generation and Differentiation of this lineage of cells, we performed in vitro studies on the Differentiation of embryonic stem cells. Materials and Methods We examined the potential of mutant embryonic stem cell lines harboring targeted deletions of the GATA-1 , FOG , SCL/tal-1 , or GATA-2 genes to differentiate into Osteoclasts and determined when these molecules function in Osteoclast development. Results The lack of GATA-1 or FOG did not affect Osteoclastogenesis. In contrast, SCL/tal-1 -null embryonic stem cells generated no Osteoclasts. In the case of the loss of GATA-2, a small number of Osteoclasts were generated. GATA-2 -null Osteoclasts were morphologically normal and the terminal maturation was not disturbed, but a defect was observed in the generation of Osteoclast progenitors. Experiments using specific inhibitors that block the signaling through macrophage colony-stimulating Factor and Osteoclast Differentiation Factor/osteoprotegerin ligand suggested that GATA-2 seems to act earlier in Osteoclastogenesis than these cytokines. Interestingly, macrophage colony-forming units were not severely reduced by the loss of GATA-2 compared to Osteoclast progenitors . Conclusion These results indicate that osteocalsts need SCL/tal-1 at an early point in development, and that GATA-2 is required for generation of Osteoclast progenitors but not for the later stages when macrophage colony-stimulating Factor and Osteoclast Differentiation Factor/osteoprotegerin ligand are needed. We also demonstrated that Osteoclast progenitors behave as a different population than macrophage colony-forming units.
Kazuki Yano - One of the best experts on this subject based on the ideXlab platform.
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Transgenic mice overexpressing soluble Osteoclast Differentiation Factor (sODF) exhibit severe osteoporosis.
Journal of bone and mineral metabolism, 2002Co-Authors: Atsuko Mizuno, Kazuki Yano, Masahiko Kinosaki, Kyoji Yamaguchi, Osamu Shibata, Takeshi Kanno, Masaki Hoshi, Nobuaki Fujise, Eisuke Tsuda, Akihiko MurakamiAbstract:Osteoclast Differentiation Factor, ODF, also called RANKL, TRANCE, or OPGL, is a key molecule for Osteoclast Differentiation and activation, and is thought to act as a membrane-associated molecule in bone remodeling. Recent study suggested that soluble ODF (sODF) released from T cells also has some roles in bone resorption. To investigate the physiological and pathological function of sODF, we generated two types of transgenic mice overexpressing sODF. Mice overexpressing sODF ubiquitously from the early developmental stage died at the late fetal stage. The other type of mice, expressing sODF only in the liver after birth, grew to maturity with normal body size and weight. However, they exhibited a marked decrease in bone mineral density with aging compared with their non-transgenic littermates, and in addition, the strength of their femurs was extremely reduced. Histological analysis showed that the trabecular bone mass was decreased at 6 weeks of age and was sparse at age 3-4 months. The number of Osteoclasts was significantly increased, while the number of osteoblasts was not altered on the surface of young trabecular bone. These results indicate that excessive production of sODF causes osteoporosis by accelerated Osteoclastogenesis. The transgenic mouse overexpressing sODF in the liver could serve as a useful animal model for studying bone remodeling and evaluating therapeutic agents for osteoporosis.
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increased circulating levels of Osteoclastogenesis inhibitory Factor osteoprotegerin in patients with chronic renal failure
American Journal of Kidney Diseases, 2002Co-Authors: Junichiro James Kazama, Kazuki Yano, Eisuke Tsuda, Takashi Shigematsu, Masakazu Miura, Yoshiko Iwasaki, Yoshindo Kawaguchi, Fumitake Gejyo, Kiyoshi Kurokawa, Masafumi FukagawaAbstract:Abstract Skeletal resistance to parathyroid hormone (PTH) is one of the major abnormalities underlying bone diseases in uremia, the mechanism of which has not yet been fully elucidated. Osteoclastogenesis inhibitory Factor (OCIF), or osteoprotegerin, is a natural decoy receptor for Osteoclast Differentiation Factor (ODF), produced by osteoblasts in response to PTH. To elucidate the kinetics and roles of OCIF in chronic renal failure, serum OCIF levels were measured in 46 predialysis patients and 21 dialysis patients by means of enzyme-linked immunosorbent assay (ELISA). Serum OCIF levels in predialysis patients increased as renal function declined (OCIF = 1.178 + 0.233 × creatinine; r 2 = 0.413; P r 2 = 0.425; P r 2 = 0.829; P 2002 by the National Kidney Foundation, Inc.
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Interactions between cancer and bone marrow cells induce Osteoclast Differentiation Factor expression and Osteoclast-like cell formation in vitro.
Biochemical and biophysical research communications, 2000Co-Authors: Noriko Chikatsu, Kazuki Yano, Eisuke Tsuda, Yasuhiro Takeuchi, Yasuhiro Tamura, Seiji Fukumoto, Etsuro Ogata, Toshiro FujitaAbstract:Cancer cells metastasized to bone induce Osteoclastogenesis for bone destruction. Coculture of either mouse melanoma B16 or breast cancer Balb/c-MC cells with mouse bone marrow cells (BMCs) induced Osteoclast-like cells, which were not observed when cancer cells were segregated from BMCs. Osteoclast Differentiation Factor (ODF), also known as receptor activator of NF-kappaB ligand (RANKL), is a direct mediator of many osteotropic Factors. Neither BMCs, B16 nor Balb/c-MC cells alone expressed ODF mRNA. However, coculture of these cancer cells with BMCs induced ODF expression, which was prevented by indomethacin. Moreover, the coculture with cancer cells inhibited secretion of osteoprotegerin/Osteoclastogenesis inhibitory Factor (OPG/OCIF), an inhibitory decoy receptor for ODF, from BMCs. Thus, enhanced Osteoclastogenesis in the presence of cancer cells might be due to an increase in ODF activity. These results suggest that interactions between cancer cells and BMCs induce ODF expression and suppress OPG/OCIF level in metastatic foci resulting in pathological Osteoclastogenesis for bone destruction.
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Basic Fibroblast Growth Factor Inhibits Osteoclast Formation Induced by 1α,25-Dihydroxyvitamin D3 through Suppressing the Production of Osteoclast Differentiation Factor☆
Biochemical and biophysical research communications, 1999Co-Authors: Nobuaki Nakagawa, Shinichi Mochizuki, Kazuki Yano, Tomonori Morinaga, Hisataka Yasuda, Kyoji Yamaguchi, Nobuyuki Shima, Naoki Kobayashi, Hitoshi Fujimoto, Kanji HigashioAbstract:Abstract Basic fibroblast growth Factor (bFGF) inhibited Osteoclast-like cell (OCL) formation in cocultures of mouse spleen cells with either osteoblasts or a stromal cell line, ST2, in the presence of 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]. bFGF directly acted on osteoblasts/stromal cells, but not Osteoclast progenitors, to inhibit 1,25(OH) 2 D 3 -induced OCL formation. bFGF suppressed the mRNA expression of Osteoclast Differentiation Factor (ODF) but did not affect that of Osteoclastogenesis inhibitory Factor (OCIF) in ST2 cells treated with 1,25(OH) 2 D 3 and dexamethasone. Enzyme-linked immunosorbent assay showed that bFGF hardly affected OCIF production in the treated ST2 cells. A genetically engineered soluble form of ODF, but not anti-OCIF neutralizing antibody, abolished bFGF-mediated inhibition of OCL formation. bFGF suppressed the binding of 125 I-labeled OCIF to both ST2 cells and osteoblasts treated with 1,25(OH) 2 D 3 . These findings indicate that bFGF inhibits 1,25(OH) 2 D 3 -induced OCL formation via suppression of ODF production by osteoblasts/stromal cells.
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Basic fibroblast growth Factor induces Osteoclast formation by reciprocally regulating the production of Osteoclast Differentiation Factor and Osteoclastogenesis inhibitory Factor in mouse osteoblastic cells.
Biochemical and biophysical research communications, 1999Co-Authors: Nobuaki Nakagawa, Shinichi Mochizuki, Kazuki Yano, Tomonori Morinaga, Hisataka Yasuda, Nobuyuki Shima, Naoki Kobayashi, Hitoshi Fujimoto, Daichi Chikazu, Hiroshi KawaguchiAbstract:Abstract Basic fibroblast growth Factor (bFGF) induced Osteoclast formation in co-cultures of mouse spleen cells and osteoblasts. Osteoclastogenesis inhibitory Factor (OCIF) and a selective cyclooxygenase-2 (COX-2) inhibitor, NS-398, abolished bFGF-induced Osteoclast formation. bFGF did not affect spleen cells, but it did affect osteoblasts, to stimulate Osteoclast formation. Northern blot analysis revealed that bFGF up-regulated the expression of Osteoclast Differentiation Factor (ODF) and COX-2 and down-regulated the expression of OCIF in primary osteoblastic cells. NS-398 abolished the increase of ODF mRNA, but it had no effect on the decrease of OCIF mRNA. NS-398 suppressed the binding of 125I-labeled OCIF to osteoblastic cells treated with bFGF. Enzyme-linked immunosorbent assay showed that bFGF inhibited OCIF production by osteoblastic cells, and the inhibition was not affected by NS-398. We conclude that bFGF induces Osteoclast formation by stimulating ODF production through COX-2-mediated prostaglandin synthesis and by suppressing OCIF production through a mechanism independent of prostaglandin synthesis.
