Compositions, Methods And Kits Relating To Remodel

The invention relates to novel nucleic acids encoding a mammalian adventitia inducible and bone expressed gene designated REMODEL, and proteins encoded thereby, whose expression is increased in certain diseases, disorders, or conditions, including, but not limited to, negative remodeling, arterial restenosis, vessel injury, ectopic ossification, fibrosis, and the like. REMODEL also plays a role in cell-cell and cell-matrix adhesion, bone density, bone formation, dorsal closure, and is associated with spina bifida-like phenotype. The invention further relates to methods of treating and detecting these diseases, disorders or conditions, comprising modulating or detecting REMODEL expression and/or production of REMODEL polypeptide

Methods For Treating Metabolic Syndrome With Cthrc1 Polypeptide

The present invention features compositions and methods for treating and preventing a metabolic syndrome featuring the collagen triple helix repeat containing-1 (Cthrc1) protein

Kit for Detecting CTHRC1 in a Sample

The invention provides methods for the treatment of coronary heart disease, peripheral vascular disease, stroke, and ischemia featuring agents that interfere with the expression or activity of Cthrc1. The invention also provides the use of Cthrc1 peptide as a therapeutic agent for the treatment of acute or chronic cardiac deficiencies. The invention further provides detection and monitoring of Cthrc1 peptide in blood or serum to assess or monitor cardiac function

Evidence for CTHRC1 Cleavage and Role in Promoting Metabolic Efficiency: Potential Implications for Endurance Athletic Performance

CTHRC1 is a secreted protein that is cleaved in both in vitro and in vivo conditions, and cleavage may be due to protease activity. We hypothesize that cell injury or cell death is associated with the release of a protease that could cleave CTHRC1, allowing for the generation of active CTHRC1 at sites of tissue injury, including myocardial infarction.https://knowledgeconnection.mainehealth.org/lambrew-retreat-2023/1016/thumbnail.jp

Copper Chelation Represses the Vascular Response to Injury

The induction of an acute inflammatory response followed by the release of polypeptide cytokines and growth factors from peripheral blood monocytes has been implicated in mediating the response to vascular injury. Because the Cu2+-binding proteins IL-1alpha and fibroblast growth factor 1 are exported into the extracellular compartment in a stress-dependent manner by using intracellular Cu2+ to facilitate the formation of S100A13 heterotetrameric complexes and these signal peptideless polypeptides have been implicated as regulators of vascular injury in vivo, we examined the ability of Cu2+ chelation to repress neointimal thickening in response to injury. We observed that the oral administration of the Cu2+ chelator tetrathiomolybdate was able to reduce neointimal thickening after balloon injury in the rat. Interestingly, although immunohistochemical analysis of control neointimal sections exhibited prominent staining for MAC1, IL-1alpha, S100A13, and the acidic phospholipid phosphatidylserine, similar sections obtained from tetrathiomolybdate-treated animals did not. Further, adenoviral gene transfer of the IL-1 receptor antagonist during vascular injury also significantly reduced the area of neointimal thickening. Our data suggest that intracellular copper may be involved in mediating the response to injury in vivo by its ability to regulate the stress-induced release of IL-1alpha by using the nonclassical export mechanism employed by human peripheral blood mononuclear cells in vitro

ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression

SummaryWe show that combinatorial mouse alleles for the secreted metalloproteases Adamts5, Adamts20 (bt), and Adamts9 result in fully penetrant soft-tissue syndactyly. Interdigital webs in Adamts5−/−;bt/bt mice had reduced apoptosis and decreased cleavage of the proteoglycan versican; however, the BMP-FGF axis, which regulates interdigital apoptosis was unaffected. BMP4 induced apoptosis, but without concomitant versican proteolysis. Haploinsufficiency of either Vcan or Fbln1, a cofactor for versican processing by ADAMTS5, led to highly penetrant syndactyly in bt mice, suggesting that cleaved versican was essential for web regression. The local application of an aminoterminal versican fragment corresponding to ADAMTS-processed versican, induced cell death in Adamts5−/−;bt/bt webs. Thus, ADAMTS proteases cooperatively maintain versican proteolysis above a required threshold to create a permissive environment for apoptosis. The data highlight the developmental significance of proteolytic action on the ECM, not only as a clearance mechanism, but also as a means to generate bioactive versican fragments

Functional study of CTHRC1 on skeletal muscle regeneration and skeletal muscle stem cells

Purpose/Background: CTHRC1 is a secreted protein highly induced in tissues undergoing repair and remodeling. Osteogenic differentiation of osteoblasts in vitro revealed that endogenously expressed CTHRC1 promotes bone formation by affecting both proliferation and differentiation. Our recent study demonstrated that CTHRC1 also inhibits osteoclastogenic differentiation, thereby playing a key role in balancing bone formation with bone resorption in vivo. However, its function on skeletal muscle stem cell and skeletal muscle regeneration is still remains unknown. Methods/Approach: In vitro culture of skeletal muscle stem cell isolated from wildtype and Cthrc1 mutant mice. Western blotting, Immuno-histological staining, Flow cytometry analysis, and RT-PCR assay are conducted. Results: Cthrc1 is transiently expressed in regenerating muscle with peak expression seen 7 days after injury. In primary cultured satellite cells, Cthrc1 is expressed in activated proliferating cells, and dramatically decreased under myogenic differentiation conditions. Comparing satellite cells isolated from Cthrc1 mutant and wildtype mice, there is no cell autonomous effect on cell proliferation (as determined by Ki67 immunofluorescence staining and EdU incorporation). Flow cytometric data showing that cell cycle progression is not affected by CTHRC1. Cthrc1 mutant cells differentiate more rapidly than wildtype cells under myogenic differentiation condition, which is supported by a significant down-regulation of myogenic determination factors, MyoD1 and myogenin, at both protein and mRNA level. In the cardiotoxin-induced muscle injury model, Cthrc1 impacted the time course of regeneration with myofiber size being increased in skeletal muscle of Cthrc1 mutant mice 10 days after injury; however, the final regenerated muscle size was significantly smaller in mutant mice 61 days after injury. Conclusions: Collectively our data indicate that Cthrc1 functions as a negative regulator on myogenic differentiation in vitro, and it is essential for successful regeneration of injured skeletal muscle