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

• Published in: Matrix biology Vol. 125; pp. 59 - 72
• Main Authors: Ackerman, Jessica E., Muscat, Samantha N., Adjei-Sowah, Emmanuela, Korcari, Antonion, Nichols, Anne E.C., Buckley, Mark R., Loiselle, Alayna E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-01-2024
• Subjects: Cell Differentiation; Cicatrix - metabolism; Extracellular matrix; Fibrosis; Humans; Myofibroblasts - metabolism; Periostin; Scar tissue; Tendon; Tendons; Extracellular matrix; Scar tissue; Periostin; Tendon
• ISSN: 0945-053X; 1569-1802
• DOI: 10.1016/j.matbio.2023.12.004

•Periostin-lineage cells contribute to a transient but not persistent myofibroblast population.•Periostin serves as a supportive niche for myofibroblast differentiation.•Periostin is required for functional tendon healing.
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 αSMA+ stress fibers, αSMA is expressed in other cell types including the vasculature. As such, modulation of myofibroblast dynamics via disruption of αSMA 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 αSMA+ 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.