دورية أكاديمية
Discoidin domain receptor 2 regulates aberrant mesenchymal lineage cell fate and matrix organization.
العنوان: | Discoidin domain receptor 2 regulates aberrant mesenchymal lineage cell fate and matrix organization. |
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المؤلفون: | Pagani CA; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA., Bancroft AC; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA., Tower RJ; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA., Livingston N; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA., Sun Y; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA., Hong JY; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA., Kent RN 3rd; Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA., Strong AL; Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA., Nunez JH; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA., Medrano JMR; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA., Patel N; Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA., Nanes BA; Department of Dermatology, University of Texas Southwestern, Dallas, TX, USA.; Lydia Hill Department of Bioinformatics, University of Texas Southwestern, Dallas, TX, USA., Dean KM; Lydia Hill Department of Bioinformatics, University of Texas Southwestern, Dallas, TX, USA.; Cecil H. and The Ida Green Center for Systems Biology, University of Texas Southwestern, Dallas, TX, USA., Li Z; Department of Pathology, Johns Hopkins University, Baltimore, MD, USA., Ge C; School of Dentistry, University of Michigan, Ann Arbor, MI, USA., Baker BM; Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA., James AW; Department of Pathology, Johns Hopkins University, Baltimore, MD, USA., Weiss SJ; Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA., Franceschi RT; School of Dentistry, University of Michigan, Ann Arbor, MI, USA., Levi B; Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA. |
المصدر: | Science advances [Sci Adv] 2022 Dec 21; Vol. 8 (51), pp. eabq6152. Date of Electronic Publication: 2022 Dec 21. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]- |
مواضيع طبية MeSH: | Discoidin Domain Receptor 2*/genetics, Mice ; Animals ; Proteomics ; Cell Differentiation/genetics ; Extracellular Matrix/metabolism ; Signal Transduction/physiology |
مستخلص: | Extracellular matrix (ECM) interactions regulate both the cell transcriptome and proteome, thereby determining cell fate. Traumatic heterotopic ossification (HO) is a disorder characterized by aberrant mesenchymal lineage (MLin) cell differentiation, forming bone within soft tissues of the musculoskeletal system following traumatic injury. Recent work has shown that HO is influenced by ECM-MLin cell receptor signaling, but how ECM binding affects cellular outcomes remains unclear. Using time course transcriptomic and proteomic analyses, we identified discoidin domain receptor 2 (DDR2), a cell surface receptor for fibrillar collagen, as a key MLin cell regulator in HO formation. Inhibition of DDR2 signaling, through either constitutive or conditional Ddr2 deletion or pharmaceutical inhibition, reduced HO formation in mice. Mechanistically, DDR2 perturbation alters focal adhesion orientation and subsequent matrix organization, modulating Focal Adhesion Kinase (FAK) and Yes1 Associated Transcriptional Regulator and WW Domain Containing Transcription Regulator 1 (YAP/TAZ)-mediated MLin cell signaling. Hence, ECM-DDR2 interactions are critical in driving HO and could serve as a previously unknown therapeutic target for treating this disease process. |
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معلومات مُعتمدة: | R01 GM123069 United States GM NIGMS NIH HHS; RM1 GM145399 United States GM NIGMS NIH HHS; U54 CA268072 United States CA NCI NIH HHS; R01 AR071379 United States AR NIAMS NIH HHS; R01 AR078324 United States AR NIAMS NIH HHS; R21 DE029012 United States DE NIDCR NIH HHS; P30 CA142543 United States CA NCI NIH HHS; T32 AR065969 United States AR NIAMS NIH HHS; T32 DE007057 United States DE NIDCR NIH HHS; T32 CA009672 United States CA NCI NIH HHS; R21 HD105189 United States HD NICHD NIH HHS; R01AR071379 United States AR NIAMS NIH HHS; R01 DK127589 United States DK NIDDK NIH HHS; P30 AR069620 United States AR NIAMS NIH HHS; P30 DK020572 United States DK NIDDK NIH HHS; R01 DE029465 United States DE NIDCR NIH HHS |
المشرفين على المادة: | EC 2.7.10.1 (Discoidin Domain Receptor 2) |
تواريخ الأحداث: | Date Created: 20221221 Date Completed: 20221223 Latest Revision: 20240510 |
رمز التحديث: | 20240510 |
مُعرف محوري في PubMed: | PMC9770942 |
DOI: | 10.1126/sciadv.abq6152 |
PMID: | 36542719 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2375-2548 |
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DOI: | 10.1126/sciadv.abq6152 |