NF-κB activation persists into the remodeling phase of tendon healing and promotes myofibroblast survival.

Journal Article (Journal Article)

Although inflammation is necessary during the early phases of tissue repair, persistent inflammation contributes to fibrosis. Acute tendon injuries often heal through a fibrotic mechanism, which impedes regeneration and functional recovery. Because inflammation mediated by nuclear factor κB (NF-κB) signaling is implicated in this process, we examined the spatial, temporal, and cell type-specific activation profile of canonical NF-κB signaling during tendon healing. NF-κB signaling was maintained through all phases of tendon healing in mice, including the remodeling phase, and tenocytes and myofibroblasts from the Scleraxis (Scx) lineage were the predominant populations that retained NF-κB activation into the late stages of repair. We confirmed persistent NF-κB activation in myofibroblasts in human tendon scar tissue. Deleting the canonical NF-κB kinase, IKKβ, in Scx-lineage cells in mice increased apoptosis and the deposition of the matrix protein periostin during the late stages of tendon repair, suggesting that persistent NF-κB signaling may facilitate myofibroblast survival and fibrotic progression. Consistent with this, myofibroblasts in human tendon scar samples displayed enhanced prosurvival signaling compared to control tissue. Together, these data suggest that NF-κB may contribute to fibrotic tendon healing through both inflammation-dependent and inflammation-independent functions, such as NF-κB-mediated cell survival.

Full Text

Duke Authors

Cited Authors

  • Best, KT; Nichols, AEC; Knapp, E; Hammert, WC; Ketonis, C; Jonason, JH; Awad, HA; Loiselle, AE

Published Date

  • November 17, 2020

Published In

Volume / Issue

  • 13 / 658

PubMed ID

  • 33203721

Pubmed Central ID

  • PMC7717665

Electronic International Standard Serial Number (EISSN)

  • 1937-9145

Digital Object Identifier (DOI)

  • 10.1126/scisignal.abb7209

Language

  • eng

Conference Location

  • United States