The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Anja-katrin Bosserhoff - One of the best experts on this subject based on the ideXlab platform.
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modulation of Cartilage Differentiation by melanoma inhibiting activity Cartilage derived retinoic acid sensitive protein mia cd rap
Experimental and Molecular Medicine, 2010Co-Authors: Thomas Schubert, Jacqueline Schlegel, Rainer Schmid, Alfred Opolka, Susanne Grässel, Martin J Humphries, Anja-katrin BosserhoffAbstract:Melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from malignant melanoma cells and from chondrocytes. Recently, we revealed that MIA/CD-RAP can modulate bone morphogenetic protein (BMP)2-induced osteogenic Differentiation into a chondrogenic direction. In the current study we aimed to find the molecular details of this MIA/CD-RAP function. Direct influence of MIA on BMP2 by protein-protein-interaction or modulating SMAD signaling was ruled out experimentally. Instead, we revealed inhibition of ERK signaling by MIA/CD-RAP. This inhibition is regulated via binding of MIA/CD-RAP to integrin α5 and abolishing its activity. Active ERK signaling is known to block chondrogenic Differentiation and we revealed induction of aggrecan expression in chondrocytes by treatment with MIA/CD-RAP or PD098059, an ERK inhibitor. In in vivo models we could support the role of MIA/CD-RAP in influencing osteogenic Differentiation negatively. Further, MIA/CD-RAP-deficient mice revealed an enhanced calcified Cartilage layer of the articular Cartilage of the knee joint and disordered arrangement of chondrocytes. Taken together, our data indicate that MIA/CD-RAP stabilizes Cartilage Differentiation and inhibits Differentiation into bone potentially by regulating signaling processes during Differentiation.
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Modulation of Cartilage Differentiation by melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP)
Experimental & Molecular Medicine, 2010Co-Authors: Thomas Schubert, Jacqueline Schlegel, Rainer Schmid, Alfred Opolka, Susanne Grässel, Martin Humphries, Anja-katrin BosserhoffAbstract:Melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from malignant melanoma cells and from chondrocytes. Recently, we revealed that MIA/CD-RAP can modulate bone morphogenetic protein (BMP)2-induced osteogenic Differentiation into a chondrogenic direction. In the current study we aimed to find the molecular details of this MIA/CD-RAP function. Direct influence of MIA on BMP2 by protein-protein-interaction or modulating SMAD signaling was ruled out experimentally. Instead, we revealed inhibition of ERK signaling by MIA/CD-RAP. This inhibition is regulated via binding of MIA/CD-RAP to integrin α5 and abolishing its activity. Active ERK signaling is known to block chondrogenic Differentiation and we revealed induction of aggrecan expression in chondrocytes by treatment with MIA/CD-RAP or PD098059, an ERK inhibitor. In in vivo models we could support the role of MIA/CD-RAP in influencing osteogenic Differentiation negatively. Further, MIA/CD-RAP-deficient mice revealed an enhanced calcified Cartilage layer of the articular Cartilage of the knee joint and disordered arrangement of chondrocytes. Taken together, our data indicate that MIA/CD-RAP stabilizes Cartilage Differentiation and inhibits Differentiation into bone potentially by regulating signaling processes during Differentiation.
Robert A. Kosher - One of the best experts on this subject based on the ideXlab platform.
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heparan sulfate proteoglycans including syndecan 3 modulate bmp activity during limb Cartilage Differentiation
Matrix Biology, 2006Co-Authors: Melanie C Fisher, Yingcui Li, Reza M Seghatoleslami, Caroline N Dealy, Robert A. KosherAbstract:Bone morphogenetic proteins (BMPs) are involved in multiple aspects of limb development including regulation of Cartilage Differentiation. Several BMPs bind strongly to heparin, and heparan sulfate proteoglycans (HSPGs) at the cell surface or in the extracellular matrix have recently been implicated as modulators of BMP signaling in some developing systems. Here we have explored the role of HSPGs in regulating BMP activity during limb chondrogenesis by evaluating the effects of exogenous heparan sulfate (HS), heparitinase treatment, and overexpression of the HSPG syndecan-3 on the ability of BMP2 to modulate the chondrogenic Differentiation of limb mesenchymal cells in micromass culture. Exogenous HS dramatically enhances the ability of BMP2 to stimulate chondrogenesis and Cartilage specific gene expression, and reduces the concentration of BMP2 needed to stimulate chondrogenesis. Furthermore, HS stimulates BMP2-mediated phosphorylation of Smad1, Smad5, and Smad8, transcriptional mediators of BMP2 signaling, indicating that HS enhances the interaction of BMP2 with its receptors. Pretreatment of micromass cultures with heparitinase to degrade endogenous HSPGs also enhances the chondrogenic activity of BMP2, and reduces the concentration of BMP2 needed to promote chondrogenesis. Taken together these results indicate that exogenous HS or heparitinase enhance the chondrogenic activity of BMP2 by interfering with its interaction with endogenous HSPGs that would normally restrict its interaction with its receptors. Consistent with the possibility that HSPGs are negative modulators of BMP signaling during chondrogenesis, we have found that overexpression of syndecan-3, which is one of the major HSPGs normally expressed during chondrogenesis, greatly impairs the ability of BMP2 to promote Cartilage Differentiation. Furthermore, retroviral overexpression of syndecan-3 inhibits BMP2-mediated Smad phosphorylation in the regions of the cultures in which chondrogenesis is inhibited and in which ectopic syndecan-3 protein is highly expressed. These results indicate that syndecan-3 interferes with the interaction of BMP2 with its receptors, and that this interference results in an inhibition of chondrogenesis. Taken together these results indicate that HSPGs including syndecan-3 normally modulate the strength of BMP signaling during limb Cartilage Differentiation by limiting the effective concentration of BMP available for signaling.
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Inhibition of in vitro limb Cartilage Differentiation by syndecan‐3 antibodies
Developmental Dynamics, 1996Co-Authors: M. Reza Seghatoleslami, Robert A. KosherAbstract:: The transmembrane heparan sulfate proteoglycan syndecan-3 is transiently expressed in high amounts during the cellular condensation process that characterizes the onset of limb Cartilage Differentiation. During condensation, limb mesenchymal cells become closely juxtaposed and undergo cell-cell and cell-matrix interactions that are necessary to trigger Cartilage Differentiation and Cartilage-specific gene expression. To test directly the possible involvement of syndecan-3 in regulating the onset of limb chondrogenesis, we examined the effect of polyclonal antibodies against a syndecan-3 fusion protein on the chondrogenic Differentiation of chick limb mesenchymal cells in micromass culture. Syndecan-3 antiserum elicits a dose-dependent inhibition of the accumulation of Alcian blue-stainable Cartilage matrix by high density limb mesenchymal cell micromass cultures (2 x 10(5) cells/10 microliters) and a corresponding reduction in steady-state levels of mRNAs for Cartilage-characteristic type II collagen and the core protein of the Cartilage proteoglycan aggrecan. In preimmune serum-treated control cultures proliferating cells are limited to the periphery of areas of Cartilage matrix deposition, whereas large numbers of proliferating cells are uniformly distributed throughout the undifferentiated cultures supplemented with syndecan-3 antiserum. Limb mesenchymal cells cultured at lower densities (1 x 10(5) cells/10 microliters) in the presence of preimmune serum form extensive preCartilage condensations characterized by the close juxtaposition of rounded cells by day 2 of culture. In contrast, in the presence of syndecan-3 antiserum, the cells fail to aggregate but rather remain flattened and spatially separated from one another, suggeting that syndecan-3 antibodies impair the formation of preCartilage condensations. These results indicate that syndecan-3 plays an important role in regulating the onset of limb chondrogenesis, perhaps by mediating the cell-cell and cell-matrix interactions required for condensation and subsequent Cartilage Differentiation.
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the expression pattern of the distal less homeo containing gene dlx 5 in the developing chick limb bud suggests its involvement in apical ectodermal ridge activity pattern formation and Cartilage Differentiation
Mechanisms of Development, 1995Co-Authors: Deborah Ferrari, William B. Upholt, Lauro Sumoy, Jennifer Gannon, Anthony M C Brown, Robert A. KosherAbstract:Abstract Here we report the isolation from a chick limb bud cDNA library of a cDNA that contains the full coding sequence of chicken Dlx-5, a member of the Distal-less (Dlx) family of homeo☐-containing genes that encode homeodomains highly similar to that of the Drosophila Distal-less gene, a gene that is required for limb development in the Drosophila embryo. The expression pattern of Dlx-5 in the developing chick limb bud suggests that it may be involved in several aspects of limb morphogenesis. Dlx-5 is expressed in the apical ectodermal ridge (AER) which directs the outgrowth and patterning of underlying limb mesoderm. During early limb development Dlx-5 is also expressed in the mesoderm at the anterior margin of the limb bud and in a discrete group of mesodermal cells at the mid-proximal posterior margin that corresponds to the posterior necrotic zone. These mesodermal domains of Dlx-5 expression roughly correspond to the anterior and posterior boundaries of the progress zone, the group of highly proliferating undifferentiated mesodermal cells underneath the AER that will give rise to the skeletal elements of the limb and associated structures. The AER and anterior and posterior mesodermal domains of Dlx-5 expression are regions in which the homeo☐-containing gene Msx-2 is also highly expressed, suggesting that Dlx-5 and Msx-2 might be involved in regulatory networks that control AER activity and demarcate the progress zone. In addition, Dlx-5 is expressed in high amounts by the differentiating cartilaginous skeletal elements of the limb, suggesting it may be involved in regulating the onset of limb Cartilage Differentiation.
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Type IX Collagen Gene Expression During Limb Cartilage Differentiation
Matrix, 1991Co-Authors: William M. Kulyk, Caroline N.d. Coelho, Robert A. KosherAbstract:Abstract Changes in the steady-state levels of mRNAs for the al(IX) and a2(IX) polypeptide chains of Cartilage-characteristic type IX collagen were examined during the course of chick limb chondrogenesis in vitro and in vivo. Cytoplasmic type IX collagen mRNAs begin to accumulate at the onset of overt chondrogenesis in high density micromass culture coincident with the crucial condensation phase of the process, in which prechondrogenic mesenchymal cells become closely juxtaposed prior to depositing a Cartilage matrix. The initiation of type IX collagen mRNA accumulation at condensation coincides with the initiation of accumulation of Cartilage proteoglycan core protein mRNA and with a striking increase in type II collagen mRNA accumulation. Following condensation in vitro, there is a concomitant progressive increase in cytoplasmic type IX collagen, core protein, and type II collagen mRNA levels which parallels the progressive accumulation of Cartilage matrix. Type IX collagen mRNAs also begin to accumulate at the initiation of overt chondrogenesis in vivo in the chondrogenic central core of the developing limb bud. In contrast, little, or no type IX collagen mRNAs are detectable in the nonchondrogenic peripheral regions of the developing limb bud.
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Role of the Transforming Growth Factor- β (TGF- β ) Family, Extracellular Matrix, and GAP Junctional Communication in Limb Cartilage Differentiation
Developmental Patterning of the Vertebrate Limb, 1991Co-Authors: Robert A. Kosher, Eileen F Roark, Stephen E. Gould, Caroline N.d. CoelhoAbstract:The Differentiation of limb mesenchymal cells into chondrocytes involves a sequential series of regulatory events mediated in part by extracellular matrix macromolecules, peptide growth factors, cell-cell and cell-matrix interactions, cytoskeletal reorganization, and intracellular second messengers such as cAMP. In the present manuscript we describe some of our current studies on the role of and the possible relationship between the TGF-β family of growth factors and extracellular matrix and cell surface molecules including the membrane-intercalated proteoglycan, syndecan in the regulation of chick limb Cartilage Differentiation. We also describe studies indicating that intercellular communication via gap junctions may be involved in the regulation of chondrogenesis.
Thomas Schubert - One of the best experts on this subject based on the ideXlab platform.
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modulation of Cartilage Differentiation by melanoma inhibiting activity Cartilage derived retinoic acid sensitive protein mia cd rap
Experimental and Molecular Medicine, 2010Co-Authors: Thomas Schubert, Jacqueline Schlegel, Rainer Schmid, Alfred Opolka, Susanne Grässel, Martin J Humphries, Anja-katrin BosserhoffAbstract:Melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from malignant melanoma cells and from chondrocytes. Recently, we revealed that MIA/CD-RAP can modulate bone morphogenetic protein (BMP)2-induced osteogenic Differentiation into a chondrogenic direction. In the current study we aimed to find the molecular details of this MIA/CD-RAP function. Direct influence of MIA on BMP2 by protein-protein-interaction or modulating SMAD signaling was ruled out experimentally. Instead, we revealed inhibition of ERK signaling by MIA/CD-RAP. This inhibition is regulated via binding of MIA/CD-RAP to integrin α5 and abolishing its activity. Active ERK signaling is known to block chondrogenic Differentiation and we revealed induction of aggrecan expression in chondrocytes by treatment with MIA/CD-RAP or PD098059, an ERK inhibitor. In in vivo models we could support the role of MIA/CD-RAP in influencing osteogenic Differentiation negatively. Further, MIA/CD-RAP-deficient mice revealed an enhanced calcified Cartilage layer of the articular Cartilage of the knee joint and disordered arrangement of chondrocytes. Taken together, our data indicate that MIA/CD-RAP stabilizes Cartilage Differentiation and inhibits Differentiation into bone potentially by regulating signaling processes during Differentiation.
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Modulation of Cartilage Differentiation by melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP)
Experimental & Molecular Medicine, 2010Co-Authors: Thomas Schubert, Jacqueline Schlegel, Rainer Schmid, Alfred Opolka, Susanne Grässel, Martin Humphries, Anja-katrin BosserhoffAbstract:Melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from malignant melanoma cells and from chondrocytes. Recently, we revealed that MIA/CD-RAP can modulate bone morphogenetic protein (BMP)2-induced osteogenic Differentiation into a chondrogenic direction. In the current study we aimed to find the molecular details of this MIA/CD-RAP function. Direct influence of MIA on BMP2 by protein-protein-interaction or modulating SMAD signaling was ruled out experimentally. Instead, we revealed inhibition of ERK signaling by MIA/CD-RAP. This inhibition is regulated via binding of MIA/CD-RAP to integrin α5 and abolishing its activity. Active ERK signaling is known to block chondrogenic Differentiation and we revealed induction of aggrecan expression in chondrocytes by treatment with MIA/CD-RAP or PD098059, an ERK inhibitor. In in vivo models we could support the role of MIA/CD-RAP in influencing osteogenic Differentiation negatively. Further, MIA/CD-RAP-deficient mice revealed an enhanced calcified Cartilage layer of the articular Cartilage of the knee joint and disordered arrangement of chondrocytes. Taken together, our data indicate that MIA/CD-RAP stabilizes Cartilage Differentiation and inhibits Differentiation into bone potentially by regulating signaling processes during Differentiation.
Susanne Grässel - One of the best experts on this subject based on the ideXlab platform.
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modulation of Cartilage Differentiation by melanoma inhibiting activity Cartilage derived retinoic acid sensitive protein mia cd rap
Experimental and Molecular Medicine, 2010Co-Authors: Thomas Schubert, Jacqueline Schlegel, Rainer Schmid, Alfred Opolka, Susanne Grässel, Martin J Humphries, Anja-katrin BosserhoffAbstract:Melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from malignant melanoma cells and from chondrocytes. Recently, we revealed that MIA/CD-RAP can modulate bone morphogenetic protein (BMP)2-induced osteogenic Differentiation into a chondrogenic direction. In the current study we aimed to find the molecular details of this MIA/CD-RAP function. Direct influence of MIA on BMP2 by protein-protein-interaction or modulating SMAD signaling was ruled out experimentally. Instead, we revealed inhibition of ERK signaling by MIA/CD-RAP. This inhibition is regulated via binding of MIA/CD-RAP to integrin α5 and abolishing its activity. Active ERK signaling is known to block chondrogenic Differentiation and we revealed induction of aggrecan expression in chondrocytes by treatment with MIA/CD-RAP or PD098059, an ERK inhibitor. In in vivo models we could support the role of MIA/CD-RAP in influencing osteogenic Differentiation negatively. Further, MIA/CD-RAP-deficient mice revealed an enhanced calcified Cartilage layer of the articular Cartilage of the knee joint and disordered arrangement of chondrocytes. Taken together, our data indicate that MIA/CD-RAP stabilizes Cartilage Differentiation and inhibits Differentiation into bone potentially by regulating signaling processes during Differentiation.
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Modulation of Cartilage Differentiation by melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP)
Experimental & Molecular Medicine, 2010Co-Authors: Thomas Schubert, Jacqueline Schlegel, Rainer Schmid, Alfred Opolka, Susanne Grässel, Martin Humphries, Anja-katrin BosserhoffAbstract:Melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from malignant melanoma cells and from chondrocytes. Recently, we revealed that MIA/CD-RAP can modulate bone morphogenetic protein (BMP)2-induced osteogenic Differentiation into a chondrogenic direction. In the current study we aimed to find the molecular details of this MIA/CD-RAP function. Direct influence of MIA on BMP2 by protein-protein-interaction or modulating SMAD signaling was ruled out experimentally. Instead, we revealed inhibition of ERK signaling by MIA/CD-RAP. This inhibition is regulated via binding of MIA/CD-RAP to integrin α5 and abolishing its activity. Active ERK signaling is known to block chondrogenic Differentiation and we revealed induction of aggrecan expression in chondrocytes by treatment with MIA/CD-RAP or PD098059, an ERK inhibitor. In in vivo models we could support the role of MIA/CD-RAP in influencing osteogenic Differentiation negatively. Further, MIA/CD-RAP-deficient mice revealed an enhanced calcified Cartilage layer of the articular Cartilage of the knee joint and disordered arrangement of chondrocytes. Taken together, our data indicate that MIA/CD-RAP stabilizes Cartilage Differentiation and inhibits Differentiation into bone potentially by regulating signaling processes during Differentiation.
Alfred Opolka - One of the best experts on this subject based on the ideXlab platform.
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modulation of Cartilage Differentiation by melanoma inhibiting activity Cartilage derived retinoic acid sensitive protein mia cd rap
Experimental and Molecular Medicine, 2010Co-Authors: Thomas Schubert, Jacqueline Schlegel, Rainer Schmid, Alfred Opolka, Susanne Grässel, Martin J Humphries, Anja-katrin BosserhoffAbstract:Melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from malignant melanoma cells and from chondrocytes. Recently, we revealed that MIA/CD-RAP can modulate bone morphogenetic protein (BMP)2-induced osteogenic Differentiation into a chondrogenic direction. In the current study we aimed to find the molecular details of this MIA/CD-RAP function. Direct influence of MIA on BMP2 by protein-protein-interaction or modulating SMAD signaling was ruled out experimentally. Instead, we revealed inhibition of ERK signaling by MIA/CD-RAP. This inhibition is regulated via binding of MIA/CD-RAP to integrin α5 and abolishing its activity. Active ERK signaling is known to block chondrogenic Differentiation and we revealed induction of aggrecan expression in chondrocytes by treatment with MIA/CD-RAP or PD098059, an ERK inhibitor. In in vivo models we could support the role of MIA/CD-RAP in influencing osteogenic Differentiation negatively. Further, MIA/CD-RAP-deficient mice revealed an enhanced calcified Cartilage layer of the articular Cartilage of the knee joint and disordered arrangement of chondrocytes. Taken together, our data indicate that MIA/CD-RAP stabilizes Cartilage Differentiation and inhibits Differentiation into bone potentially by regulating signaling processes during Differentiation.
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Modulation of Cartilage Differentiation by melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP)
Experimental & Molecular Medicine, 2010Co-Authors: Thomas Schubert, Jacqueline Schlegel, Rainer Schmid, Alfred Opolka, Susanne Grässel, Martin Humphries, Anja-katrin BosserhoffAbstract:Melanoma inhibiting activity/Cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from malignant melanoma cells and from chondrocytes. Recently, we revealed that MIA/CD-RAP can modulate bone morphogenetic protein (BMP)2-induced osteogenic Differentiation into a chondrogenic direction. In the current study we aimed to find the molecular details of this MIA/CD-RAP function. Direct influence of MIA on BMP2 by protein-protein-interaction or modulating SMAD signaling was ruled out experimentally. Instead, we revealed inhibition of ERK signaling by MIA/CD-RAP. This inhibition is regulated via binding of MIA/CD-RAP to integrin α5 and abolishing its activity. Active ERK signaling is known to block chondrogenic Differentiation and we revealed induction of aggrecan expression in chondrocytes by treatment with MIA/CD-RAP or PD098059, an ERK inhibitor. In in vivo models we could support the role of MIA/CD-RAP in influencing osteogenic Differentiation negatively. Further, MIA/CD-RAP-deficient mice revealed an enhanced calcified Cartilage layer of the articular Cartilage of the knee joint and disordered arrangement of chondrocytes. Taken together, our data indicate that MIA/CD-RAP stabilizes Cartilage Differentiation and inhibits Differentiation into bone potentially by regulating signaling processes during Differentiation.