Discoidin domain receptor 2 regulates aberrant mesenchymal lineage cell fate and matrix organization-Reference-Cited by-同舟云学术

Discoidin domain receptor 2 regulates aberrant mesenchymal lineage cell fate and matrix organization

Published:2022-12-21 Issue:51 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Pagani Chase A.¹^ORCID,Bancroft Alec C.¹^ORCID,Tower Robert J.¹^ORCID,Livingston Nicholas¹,Sun Yuxiao¹^ORCID,Hong Jonathan Y.¹^ORCID,Kent Robert N.²^ORCID,Strong Amy L.³^ORCID,Nunez Johanna H.¹,Medrano Jessica Marie R.¹^ORCID,Patel Nicole³^ORCID,Nanes Benjamin A.⁴⁵^ORCID,Dean Kevin M.⁵⁶^ORCID,Li Zhao⁷^ORCID,Ge Chunxi⁸^ORCID,Baker Brendon M.²^ORCID,James Aaron W.⁷^ORCID,Weiss Stephen J.⁹^ORCID,Franceschi Renny T.⁸^ORCID,Levi Benjamin¹^ORCID

Affiliation:

1. Center for Organogenesis and Trauma, Department of Surgery, University of Texas Southwestern, Dallas, TX, USA.

2. Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.

3. Section of Plastic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

4. Department of Dermatology, University of Texas Southwestern, Dallas, TX, USA.

5. Lydia Hill Department of Bioinformatics, University of Texas Southwestern, Dallas, TX, USA.

6. Cecil H. and The Ida Green Center for Systems Biology, University of Texas Southwestern, Dallas, TX, USA.

7. Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.

8. School of Dentistry, University of Michigan, Ann Arbor, MI, USA.

9. Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference67 articles.

1. Multilineage Potential of Adult Human Mesenchymal Stem Cells

2. Control of Stem Cell Fate by Physical Interactions with the Extracellular Matrix

3. Three-dimensional reconstituted extracellular matrix scaffolds for tissue engineering

4. Mechanical regulation of mesenchymal stem cell differentiation

5. Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels

Cited by 8 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Novel insights into the role of Discoidin domain receptor 2 (DDR2) in cancer progression: a new avenue of therapeutic intervention;Matrix Biology;2024-01

2. TrkA-mediated sensory innervation of injured mouse tendon supports tendon sheath progenitor cell expansion and tendon repair;Science Translational Medicine;2023-12-20

3. Inhibition of focal adhesion kinase 2 results in a macrophage polarization shift to M2 which attenuates local and systemic inflammation and reduces heterotopic ossification after polysystem extremity trauma;Frontiers in Immunology;2023-12-05

4. Enhanced BMP signaling in Cathepsin K-positive tendon progenitors induces heterotopic ossification;Biochemical and Biophysical Research Communications;2023-12

5. DDR2-regulated arginase activity in ovarian cancer-associated fibroblasts promotes collagen production and tumor progression;Oncogene;2023-11-23