The Experts below are selected from a list of 8424 Experts worldwide ranked by ideXlab platform

Yousef Abuamer - One of the best experts on this subject based on the ideXlab platform.

  • the iκb kinase ikk inhibitor nemo binding domain peptide blocks osteoclastogenesis and Bone Erosion in inflammatory arthritis
    Journal of Biological Chemistry, 2004
    Co-Authors: Simon Dai, Teruhisa Hirayama, Sabiha Abbas, Yousef Abuamer
    Abstract:

    Activation of NF-kappaB leads to expression of ample genes that regulate inflammatory and osteoclastogenic responses. The process is facilitated by induction of IkappaB kinase (IKK) complex that phosphorylates IkappaB and leads to its dissociation from the NF-kappaB complex, thus permitting activation of NF-kappaB. The IKK complex contains primarily IKKalpha, IKKbeta, and the regulatory kinase IKKgamma, also known as NEMO. NEMO regulates the IKK complex activity through its binding to carboxyl-terminal region of IKKalpha and IKKbeta, termed NEMO-binding domain (NBD). In this regard, a cell-permeable NBD peptide has been shown to block association of NEMO with the IKK complex and inhibit activation of NF-kappaB. Given the pivotal role of cytokine-induced NF-kappaB in osteoclastogenesis and inflammatory Bone loss, we deduced that cell-permeable TAT-NBD peptide may hinder osteoclastogenesis and Bone Erosion in inflammatory arthritis. Using NBD peptides, we show that wild type, but not mutant, NBD blocks IKK activation and reduces cytokine-induced promoter and DNA binding activities of NF-kappaB and inhibits cytokine-induced osteoclast formation by osteoclast precursors. Consistent with the key role of NF-kappaB in osteoinflammatory responses in vivo, wild type TAT-NBD administered into mice prior to induction of inflammatory arthritis efficiently block in vivo osteoclastogenesis, inhibits focal Bone Erosion, and ameliorates inflammatory responses in the joints of arthritic mice. The mutant NBD peptide fails to exert these functions. These results provide strong evidence that IKKs are potent regulators of cytokine-induced osteoclastogenesis and inflammatory arthritis. More importantly, blockade of NEMO assembly with the IKK complex is a viable strategy to avert inflammatory osteolysis.

  • the iκb kinase ikk inhibitor nemo binding domain peptide blocks osteoclastogenesis and Bone Erosion in inflammatory arthritis
    Journal of Biological Chemistry, 2004
    Co-Authors: Teruhisa Hirayama, Sabiha Abbas, Yousef Abuamer
    Abstract:

    Abstract Activation of NF-κB leads to expression of ample genes that regulate inflammatory and osteoclastogenic responses. The process is facilitated by induction of IκB kinase (IKK) complex that phosphorylates IκB and leads to its dissociation from the NF-κB complex, thus permitting activation of NF-κB. The IKK complex contains primarily IKKα, IKKβ, and the regulatory kinase IKKγ, also known as NEMO. NEMO regulates the IKK complex activity through its binding to carboxyl-terminal region of IKKα and IKKβ, termed NEMO-binding domain (NBD). In this regard, a cell-permeable NBD peptide has been shown to block association of NEMO with the IKK complex and inhibit activation of NF-κB. Given the pivotal role of cytokine-induced NF-κB in osteoclastogenesis and inflammatory Bone loss, we deduced that cell-permeable TAT-NBD peptide may hinder osteoclastogenesis and Bone Erosion in inflammatory arthritis. Using NBD peptides, we show that wild type, but not mutant, NBD blocks IKK activation and reduces cytokine-induced promoter and DNA binding activities of NF-κB and inhibits cytokine-induced osteoclast formation by osteoclast precursors. Consistent with the key role of NF-κB in osteoinflammatory responses in vivo, wild type TAT-NBD administered into mice prior to induction of inflammatory arthritis efficiently block in vivo osteoclastogenesis, inhibits focal Bone Erosion, and ameliorates inflammatory responses in the joints of arthritic mice. The mutant NBD peptide fails to exert these functions. These results provide strong evidence that IKKs are potent regulators of cytokine-induced osteoclastogenesis and inflammatory arthritis. More importantly, blockade of NEMO assembly with the IKK complex is a viable strategy to avert inflammatory osteolysis.

Teruhisa Hirayama - One of the best experts on this subject based on the ideXlab platform.

  • the iκb kinase ikk inhibitor nemo binding domain peptide blocks osteoclastogenesis and Bone Erosion in inflammatory arthritis
    Journal of Biological Chemistry, 2004
    Co-Authors: Simon Dai, Teruhisa Hirayama, Sabiha Abbas, Yousef Abuamer
    Abstract:

    Activation of NF-kappaB leads to expression of ample genes that regulate inflammatory and osteoclastogenic responses. The process is facilitated by induction of IkappaB kinase (IKK) complex that phosphorylates IkappaB and leads to its dissociation from the NF-kappaB complex, thus permitting activation of NF-kappaB. The IKK complex contains primarily IKKalpha, IKKbeta, and the regulatory kinase IKKgamma, also known as NEMO. NEMO regulates the IKK complex activity through its binding to carboxyl-terminal region of IKKalpha and IKKbeta, termed NEMO-binding domain (NBD). In this regard, a cell-permeable NBD peptide has been shown to block association of NEMO with the IKK complex and inhibit activation of NF-kappaB. Given the pivotal role of cytokine-induced NF-kappaB in osteoclastogenesis and inflammatory Bone loss, we deduced that cell-permeable TAT-NBD peptide may hinder osteoclastogenesis and Bone Erosion in inflammatory arthritis. Using NBD peptides, we show that wild type, but not mutant, NBD blocks IKK activation and reduces cytokine-induced promoter and DNA binding activities of NF-kappaB and inhibits cytokine-induced osteoclast formation by osteoclast precursors. Consistent with the key role of NF-kappaB in osteoinflammatory responses in vivo, wild type TAT-NBD administered into mice prior to induction of inflammatory arthritis efficiently block in vivo osteoclastogenesis, inhibits focal Bone Erosion, and ameliorates inflammatory responses in the joints of arthritic mice. The mutant NBD peptide fails to exert these functions. These results provide strong evidence that IKKs are potent regulators of cytokine-induced osteoclastogenesis and inflammatory arthritis. More importantly, blockade of NEMO assembly with the IKK complex is a viable strategy to avert inflammatory osteolysis.

  • the iκb kinase ikk inhibitor nemo binding domain peptide blocks osteoclastogenesis and Bone Erosion in inflammatory arthritis
    Journal of Biological Chemistry, 2004
    Co-Authors: Teruhisa Hirayama, Sabiha Abbas, Yousef Abuamer
    Abstract:

    Abstract Activation of NF-κB leads to expression of ample genes that regulate inflammatory and osteoclastogenic responses. The process is facilitated by induction of IκB kinase (IKK) complex that phosphorylates IκB and leads to its dissociation from the NF-κB complex, thus permitting activation of NF-κB. The IKK complex contains primarily IKKα, IKKβ, and the regulatory kinase IKKγ, also known as NEMO. NEMO regulates the IKK complex activity through its binding to carboxyl-terminal region of IKKα and IKKβ, termed NEMO-binding domain (NBD). In this regard, a cell-permeable NBD peptide has been shown to block association of NEMO with the IKK complex and inhibit activation of NF-κB. Given the pivotal role of cytokine-induced NF-κB in osteoclastogenesis and inflammatory Bone loss, we deduced that cell-permeable TAT-NBD peptide may hinder osteoclastogenesis and Bone Erosion in inflammatory arthritis. Using NBD peptides, we show that wild type, but not mutant, NBD blocks IKK activation and reduces cytokine-induced promoter and DNA binding activities of NF-κB and inhibits cytokine-induced osteoclast formation by osteoclast precursors. Consistent with the key role of NF-κB in osteoinflammatory responses in vivo, wild type TAT-NBD administered into mice prior to induction of inflammatory arthritis efficiently block in vivo osteoclastogenesis, inhibits focal Bone Erosion, and ameliorates inflammatory responses in the joints of arthritic mice. The mutant NBD peptide fails to exert these functions. These results provide strong evidence that IKKs are potent regulators of cytokine-induced osteoclastogenesis and inflammatory arthritis. More importantly, blockade of NEMO assembly with the IKK complex is a viable strategy to avert inflammatory osteolysis.

Sabiha Abbas - One of the best experts on this subject based on the ideXlab platform.

  • the iκb kinase ikk inhibitor nemo binding domain peptide blocks osteoclastogenesis and Bone Erosion in inflammatory arthritis
    Journal of Biological Chemistry, 2004
    Co-Authors: Simon Dai, Teruhisa Hirayama, Sabiha Abbas, Yousef Abuamer
    Abstract:

    Activation of NF-kappaB leads to expression of ample genes that regulate inflammatory and osteoclastogenic responses. The process is facilitated by induction of IkappaB kinase (IKK) complex that phosphorylates IkappaB and leads to its dissociation from the NF-kappaB complex, thus permitting activation of NF-kappaB. The IKK complex contains primarily IKKalpha, IKKbeta, and the regulatory kinase IKKgamma, also known as NEMO. NEMO regulates the IKK complex activity through its binding to carboxyl-terminal region of IKKalpha and IKKbeta, termed NEMO-binding domain (NBD). In this regard, a cell-permeable NBD peptide has been shown to block association of NEMO with the IKK complex and inhibit activation of NF-kappaB. Given the pivotal role of cytokine-induced NF-kappaB in osteoclastogenesis and inflammatory Bone loss, we deduced that cell-permeable TAT-NBD peptide may hinder osteoclastogenesis and Bone Erosion in inflammatory arthritis. Using NBD peptides, we show that wild type, but not mutant, NBD blocks IKK activation and reduces cytokine-induced promoter and DNA binding activities of NF-kappaB and inhibits cytokine-induced osteoclast formation by osteoclast precursors. Consistent with the key role of NF-kappaB in osteoinflammatory responses in vivo, wild type TAT-NBD administered into mice prior to induction of inflammatory arthritis efficiently block in vivo osteoclastogenesis, inhibits focal Bone Erosion, and ameliorates inflammatory responses in the joints of arthritic mice. The mutant NBD peptide fails to exert these functions. These results provide strong evidence that IKKs are potent regulators of cytokine-induced osteoclastogenesis and inflammatory arthritis. More importantly, blockade of NEMO assembly with the IKK complex is a viable strategy to avert inflammatory osteolysis.

  • the iκb kinase ikk inhibitor nemo binding domain peptide blocks osteoclastogenesis and Bone Erosion in inflammatory arthritis
    Journal of Biological Chemistry, 2004
    Co-Authors: Teruhisa Hirayama, Sabiha Abbas, Yousef Abuamer
    Abstract:

    Abstract Activation of NF-κB leads to expression of ample genes that regulate inflammatory and osteoclastogenic responses. The process is facilitated by induction of IκB kinase (IKK) complex that phosphorylates IκB and leads to its dissociation from the NF-κB complex, thus permitting activation of NF-κB. The IKK complex contains primarily IKKα, IKKβ, and the regulatory kinase IKKγ, also known as NEMO. NEMO regulates the IKK complex activity through its binding to carboxyl-terminal region of IKKα and IKKβ, termed NEMO-binding domain (NBD). In this regard, a cell-permeable NBD peptide has been shown to block association of NEMO with the IKK complex and inhibit activation of NF-κB. Given the pivotal role of cytokine-induced NF-κB in osteoclastogenesis and inflammatory Bone loss, we deduced that cell-permeable TAT-NBD peptide may hinder osteoclastogenesis and Bone Erosion in inflammatory arthritis. Using NBD peptides, we show that wild type, but not mutant, NBD blocks IKK activation and reduces cytokine-induced promoter and DNA binding activities of NF-κB and inhibits cytokine-induced osteoclast formation by osteoclast precursors. Consistent with the key role of NF-κB in osteoinflammatory responses in vivo, wild type TAT-NBD administered into mice prior to induction of inflammatory arthritis efficiently block in vivo osteoclastogenesis, inhibits focal Bone Erosion, and ameliorates inflammatory responses in the joints of arthritic mice. The mutant NBD peptide fails to exert these functions. These results provide strong evidence that IKKs are potent regulators of cytokine-induced osteoclastogenesis and inflammatory arthritis. More importantly, blockade of NEMO assembly with the IKK complex is a viable strategy to avert inflammatory osteolysis.

Mario Rothbauer - One of the best experts on this subject based on the ideXlab platform.

  • establishment of a human three dimensional chip based chondro synovial coculture joint model for reciprocal cross talk studies in arthritis research
    Lab on a Chip, 2021
    Co-Authors: Mario Rothbauer, Ruth A Byrne, Silvia Schobesberger, Isabel Olmos Calvo, Anita Fischer, Eva I Reihs, Sarah Spitz, Barbara Bachmann
    Abstract:

    Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane as the joint capsule's inner layer is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to Bone Erosion and cartilage destruction. While microfluidic models that model molecular aspects of Bone Erosion between Bone-derived cells and synoviocytes have been established, RA's synovial-chondral axis has not yet been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue coculture model that simulates the reciprocal cross talk between individual synovial and chondral organoids. When co-cultivated with synovial organoids, we could demonstrate that chondral organoids induce a higher degree of cartilage physiology and architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross talk in the modelling of arthritic diseases.

  • establishment of a human three dimensional chip based chondro synovial co culture joint model for reciprocal cross talk studies in arthritis research
    bioRxiv, 2021
    Co-Authors: Mario Rothbauer, Silvia Schobesberger, Anita Fischer, Eva I Reihs, Sarah Spitz, R Byrne, Olmos I Calvo, B E M Bachmann
    Abstract:

    Abstract Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane, which is the joint capsule’s inner layer, is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to Bone Erosion and cartilage destruction. While microfluidic models that model molecular aspects of Bone Erosion between Bone-derived cells and synoviocytes have been established, RA’s synovial-chondral axis has yet not been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue co-culture model that simulates the reciprocal cross-talk between individual synovial and chondral organoids. We now demonstrate that chondral organoids, when co-cultivated with synovial organoids, induce a higher degree of cartilage physiology and architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross-talk in the modelling of arthritic diseases.

Simon Dai - One of the best experts on this subject based on the ideXlab platform.

  • the iκb kinase ikk inhibitor nemo binding domain peptide blocks osteoclastogenesis and Bone Erosion in inflammatory arthritis
    Journal of Biological Chemistry, 2004
    Co-Authors: Simon Dai, Teruhisa Hirayama, Sabiha Abbas, Yousef Abuamer
    Abstract:

    Activation of NF-kappaB leads to expression of ample genes that regulate inflammatory and osteoclastogenic responses. The process is facilitated by induction of IkappaB kinase (IKK) complex that phosphorylates IkappaB and leads to its dissociation from the NF-kappaB complex, thus permitting activation of NF-kappaB. The IKK complex contains primarily IKKalpha, IKKbeta, and the regulatory kinase IKKgamma, also known as NEMO. NEMO regulates the IKK complex activity through its binding to carboxyl-terminal region of IKKalpha and IKKbeta, termed NEMO-binding domain (NBD). In this regard, a cell-permeable NBD peptide has been shown to block association of NEMO with the IKK complex and inhibit activation of NF-kappaB. Given the pivotal role of cytokine-induced NF-kappaB in osteoclastogenesis and inflammatory Bone loss, we deduced that cell-permeable TAT-NBD peptide may hinder osteoclastogenesis and Bone Erosion in inflammatory arthritis. Using NBD peptides, we show that wild type, but not mutant, NBD blocks IKK activation and reduces cytokine-induced promoter and DNA binding activities of NF-kappaB and inhibits cytokine-induced osteoclast formation by osteoclast precursors. Consistent with the key role of NF-kappaB in osteoinflammatory responses in vivo, wild type TAT-NBD administered into mice prior to induction of inflammatory arthritis efficiently block in vivo osteoclastogenesis, inhibits focal Bone Erosion, and ameliorates inflammatory responses in the joints of arthritic mice. The mutant NBD peptide fails to exert these functions. These results provide strong evidence that IKKs are potent regulators of cytokine-induced osteoclastogenesis and inflammatory arthritis. More importantly, blockade of NEMO assembly with the IKK complex is a viable strategy to avert inflammatory osteolysis.