Neer Award 2018: Platelet-derived growth factor receptor α co-expression typifies a subset of platelet-derived growth factor receptor β–positive progenitor cells that contribute to fatty degeneration and fibrosis of the murine rotator cuff
| Autor: | Sai K. Devana, Allison Ariniello, Brandon K. Vu, Bruno Péault, Ayelet Dar, Frank A. Petrigliano, Gina M Mosich, Andrew R. Jensen, Paras Shah, Claire D. Eliasberg, Benjamin V Kelley, Iain R. Murray |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Receptor Platelet-Derived Growth Factor alpha Muscle Fibers Skeletal Cell Awards and Prizes Mice Transgenic Rotator Cuff Injuries Green fluorescent protein Receptor Platelet-Derived Growth Factor beta Mice Rotator Cuff 03 medical and health sciences Growth factor receptor Fibrosis medicine Animals Orthopedics and Sports Medicine Progenitor cell Cells Cultured Adipogenesis biology business.industry Stem Cells General Medicine medicine.disease In vitro Tissue Degeneration Disease Models Animal 030104 developmental biology medicine.anatomical_structure Adipose Tissue Cancer research biology.protein Surgery Atrophy business Platelet-derived growth factor receptor |
| Zdroj: | Journal of Shoulder and Elbow Surgery. 27:1149-1161 |
| ISSN: | 1058-2746 |
| DOI: | 10.1016/j.jse.2018.02.040 |
| Popis: | Background and hypothesis After massive tears, rotator cuff muscle often undergoes atrophy, fibrosis, and fatty degeneration. These changes can lead to high surgical failure rates and poor patient outcomes. The identity of the progenitor cells involved in these processes has not been fully elucidated. Platelet-derived growth factor receptor β (PDGFRβ) and platelet-derived growth factor receptor α (PDGFRα) have previously been recognized as markers of cells involved in muscle fibroadipogenesis. We hypothesized that PDGFRα expression identifies a fibroadipogenic subset of PDGFRβ+ progenitor cells that contribute to fibroadipogenesis of the rotator cuff. Methods We created massive rotator cuff tears in a transgenic strain of mice that allows PDGFRβ+ cells to be tracked via green fluorescent protein (GFP) fluorescence. We then harvested rotator cuff muscle tissues at multiple time points postoperatively and analyzed them for the presence and localization of GFP+ PDGFRβ+ PDGFRα+ cells. We cultured, induced, and treated these cells with the molecular inhibitor CWHM-12 to assess fibrosis inhibition. Results GFP+ PDGFRβ+ PDGFRα+ cells were present in rotator cuff muscle tissue and, after massive tears, localized to fibrotic and adipogenic tissues. The frequency of PDGFRβ+ PDGFRα+ cells increased at 5 days after massive cuff tears and decreased to basal levels within 2 weeks. PDGFRβ+ PDGFRα+ cells were highly adipogenic and significantly more fibrogenic than PDGFRβ+ PDGFRα– cells in vitro and localized to adipogenic and fibrotic tissues in vivo. Treatment with CWHM-12 significantly decreased fibrogenesis from PDGFRβ+ PDGFRα+ cells. Conclusion PDGFRβ+ PDGFRα+ cells directly contribute to fibrosis and fatty degeneration after massive rotator cuff tears in the mouse model. In addition, CWHM-12 treatment inhibits fibrogenesis from PDGFRβ+ PDGFRα+ cells in vitro. Clinically, perioperative PDGFRβ+ PDGFRα+ cell inhibition may limit rotator cuff tissue degeneration and, ultimately, improve surgical outcomes for massive rotator cuff tears. |
| Databáze: | OpenAIRE |
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