Authors: Chase A. Pagani, Alec C. Bancroft, Robert J. Tower, Nicholas Livingston, Yuxiao Sun, Jonathan Y. Hong, Robert N. Kent, Amy L. Strong, Johanna H. Nunez, Jessica Marie R. Medrano, Nicole Patel, Benjamin A. Nanes, Kevin M. Dean, Zhao Li, Chunxi Ge, Brendon M. Baker, Aaron W. James, Stephen J. Weiss, Renny T. Franceschi, Benjamin Levi
Published: 2022-12-21
Source: Full article
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