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dc.contributor.authorAlmehmadi, Ahmad Hameden_US
dc.date.accessioned2019-10-22T15:27:09Z
dc.date.available2019-10-22T15:27:09Z
dc.date.issued2015
dc.date.submitted2015
dc.identifier.other(OCoLC)927114755
dc.identifier.other(OCoLC)ocn927114755
dc.identifier.urihttps://hdl.handle.net/2144/38287
dc.descriptionPLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.en_US
dc.descriptionThesis (DScD) --Boston University, Henry M. Goldman School of Dental Medicine, 2015 (Department of Molecular and Cell Biology).en_US
dc.descriptionIncludes bibliographic references: leaves 55-64.en_US
dc.description.abstractRecently, significant attention has been paid to the cysteine knot proteins (CKPs) due to their potent biological effects on transforming growth factor (TGF)-[beta] superfamily members. By a bioinformatics approach,we have identified a novel member of CKP family. VWC2 (von Willebrand factor C domain containing 2), which is previously known as Brorin. Since Brorin has been proposed to function as a bone morphogenetic protein (BMP) antagonist, we investigated the binding of Brorin/VWC2 to several BMPs; however, no binding was found. To further identify the possible target of VWC2 among TGF[beta]superfamily members, the [beta]A subunit of activin was found as a binding partner of VWC2. Our data demonstrated that Vwc2 gene expression is temporally upregulated early in osteoblast differentiation. VWC2 protein is present in bone matrix, and localized at osteoblasts/osteocytes. Activin A-induced Smad2 phosphorylation was inhibited in the presence of exogenous VWC2 in the MC3T3-E1 osteoblast cell line and in primary mouse osteoblasts. The effect of VWC2 on ex vivo cranial bone organ cultures treated with activin A was investigated, and bone morphometric parameters including total/new bone areas and width decreased by activin A were restored with VWC2 treatment. To further investigate the biological mechanism how VWC2 inhibited the effects of activin A on bone formation, osteoblast cell growth, differentiation,and mineralization were examined,and the effects of activin A on these cell functions were reversed by VWC2 treatment. Taken together, VWC2 is a novel secretory protein in bone and promotes bone formation by inhibiting Activin-Smad2 signaling pathway.en_US
dc.language.isoen_US
dc.publisherBoston Universityen_US
dc.rightsThis work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.en_US
dc.subjectOsteoblastsen_US
dc.subjectActivinsen_US
dc.subjectVwc2 protein, mouseen_US
dc.titleVWC2 increases bone formation through inhibiting activin signalingen_US
dc.typeThesis/Dissertationen_US
etd.degree.nameDoctor of Science in Dentistryen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplineMolecular and Cell Biologyen_US
etd.degree.grantorBoston Universityen_US


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