Back

Pathologic profibrotic activation of distinct myeloid cell subsets in a model of impaired healing after anterior cruciate ligament reconstruction

Morita, W.; Suzuki, Y.; Yuan, R.; Rodeo, S. A.; Park-Min, K.-H.; Ivashkiv, L. B.

2025-08-02 immunology
10.1101/2025.07.31.667715 bioRxiv
Show abstract

Anterior cruciate ligament reconstruction (ACLR) may fail due to poor bone-to-tendon integration, yet the cellular mechanisms underlying this process remain incompletely understood. Using a murine model of ACLR, we show that host-derived immune cells are the primary drivers of early healing, while tendon graft-derived stromal cells also contribute at the tendon-bone interface. We developed a model of impaired post-ACLR healing by a surgical approach, that led to increased infiltration of immune cells at the tendon-bone interface, particularly CX3CR1+ monocytes/macrophages (MonoMacs). Single-cell RNA sequencing revealed dynamic monocyte-to-macrophage transitions, with an enrichment of fibrotic, mechanosensitive CX3CR1+ MonoMacs in the impaired healing model. These findings suggest that excessive recruitment or functional shifts in host-derived MonoMacs may disrupt normal healing dynamics. Our study identifies CX3CR1+ MonoMacs as a key cell population related to inferior bone-to-tendon healing after ACLR and potential therapeutic targets to improve surgical outcomes.

Matching journals

The top 6 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.