biostudies-literatureHowell KLNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNIAMS NIH HHSe21618https://www.ebi.ac.uk/biostudies/studies/S-EPMC8228445biostudies-literatureUnknown35(6)Tendons are dense connective tissues that transmit muscle forces to the skeleton. After adult injury, healing potential is generally poor and dominated by scar formation. Although the immune response is a key feature of healing, the specific immune cells and signals that drive tendon healing have not been fully defined. In particular, the immune regulators underlying tendon regeneration are almost completely unknown due to a paucity of tendon regeneration models. Using a mouse model of neonatal tendon regeneration, we screened for immune-related markers and identified upregulation of several genes associated with inflammation, macrophage chemotaxis, and TGFβ signaling after injury. Depletion of macrophages using AP20187 treatment of MaFIA mice resulted in impaired functional healing, reduced cell proliferation, reduced ScxGFP+ neo-tendon formation, and altered tendon gene expression. Collectively, these results show that inflammation is a key component of neonatal tendon regeneration and demonstrate a requirement for macrophages in effective functional healing.FASEB journal : official publication of the Federation of American Societies for Experimental BiologyMacrophage depletion impairs neonatal tendon regeneration.PMC8228445R56AR076984R56 AR076984F31AR073626R01 AR069537F31 AR073626R01AR069537Yeoh KLi TMKaji DAMontero AHowell KLNasser PHuang AHfalseMacrophage depletion impairs neonatal tendon regeneration.Tendons are dense connective tissues that transmit muscle forces to the skeleton. After adult injury, healing potential is generally poor and dominated by scar formation. Although the immune response is a key feature of healing, the specific immune cells and signals that drive tendon healing have not been fully defined. In particular, the immune regulators underlying tendon regeneration are almost completely unknown due to a paucity of tendon regeneration models. Using a mouse model of neonatal tendon regeneration, we screened for immune-related markers and identified upregulation of several genes associated with inflammation, macrophage chemotaxis, and TGFβ signaling after injury. Depletion of macrophages using AP20187 treatment of MaFIA mice resulted in impaired functional healing, reduced cell proliferation, reduced ScxGFP+ neo-tendon formation, and altered tendon gene expression. Collectively, these results show that inflammation is a key component of neonatal tendon regeneration and demonstrate a requirement for macrophages in effective functional healing.2021-01-01T00:00:00Z2021 Jun2025-04-04T20:15:36.099Z2025-04-04T20:15:36.099ZS-EPMC82284453398233710.1096/fj.202100049R10.1096/fj.202100049r