Identification of Periostin as a critical niche for myofibroblast dynamics and fibrosis during tendon healing

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.21.550090v1?rss=1 Authors: Ackerman, J. E., Adjei-Sowah, E., Korcari, A., Muscat, S. N., Nichols, A. E., Buckley, M. R., Loiselle, A. E. Abstract: Tendon injuries are a major clinical problem, with poor patient outcomes caused by abundant scar tissue deposition during healing. Myofibroblasts play a critical role in the initial restoration of structural integrity after injury. However, persistent myofibroblast activity drives the transition to fibrotic scar tissue formation. As such, disrupting myofibroblast persistence is a key therapeutic target. While myofibroblasts are typically defined by the presence of SMA+ stress fibers, SMA is expressed in other cell types including the vasculature. As such, modulation of myofibroblast dynamics via disruption of SMA expression is not a translationally tenable approach. Recent work has demonstrated that Periostin-lineage (PostnLin) cells are a precursor for cardiac fibrosis-associated myofibroblasts. In contrast to this, here we show that PostnLin cells contribute to a transient SMA+ myofibroblast population that is required for functional tendon healing, and that Periostin forms a supportive matrix niche that facilitates myofibroblast differentiation and persistence. Collectively, these data identify the Periostin matrix niche as a critical regulator of myofibroblast fate and persistence that could be targeted for therapeutic manipulation to facilitate regenerative tendon healing. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC