Biology subjects

Kaji, D. A.

Publications and source records attributed to Kaji, D. A..

2 recordsLinked to original sources

bioRxiv2021

Macrophage 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 undetermined 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 TGF{beta} 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.

immunology↗

bioRxiv2019

TGFβ signaling is required for tenocyte recruitment and functional neonatal tendon regeneration

Tendon injuries are common with poor healing potential. The paucity of therapies for tendon is due to our limited understanding of the cells and molecules that drive tendon regeneration. Using a model of neonatal mouse tendon regeneration, we determined the molecular basis for regeneration and identify TGF{beta} signaling as a major pathway. Through targeted gene deletion, small molecule inhibition, and lineage tracing, we elucidated TGF{beta}-dependent and -independent mechanisms underyling tendon regeneration. Importantly, functional recovery depended on TGF{beta} signaling and loss of function is due to impaired tenogenic cell recruitment from both Scxlin and non-Scxlin sources. We show that TGF{beta} signaling is required directly in neonatal tenocytes for recruitment and that TGF{beta} is positively regulated in tendons. Collectively, these results are the first to show a functional role for TGF{beta} signaling in tendon regeneration and offer new insights toward the divergent cellular activities that may lead to regenerative vs fibrotic healing.

developmental biology↗