Diabetes-Induced NF-κB Dysregulation in Skeletal Stem Cells Prevents Resolution of Inflammation.

ABSTRACT: Type 1 diabetes (T1D) imposes a significant health burden by negatively affecting tissue regeneration during wound healing. The adverse effect of diabetes is attributed to high levels of inflammation, but the cellular mechanisms responsible remain elusive. In this study, we show that intrinsic skeletal stem cells (SSCs), a subset of mesenchymal stem cells, are essential for resolution of inflammation to occur during osseous healing by using genetic approaches to selectively ablate SSCs. T1D caused aberrant nuclear factor-κB (NF-κB) activation in SSCs and substantially enhanced inflammation in vivo. Constitutive or tamoxifen-induced inhibition of NF-κB in SSCs rescued the impact of diabetes on inflammation, SSC expansion, and tissue formation. In contrast, NF-κB inhibition in chondrocytes f

SUBMITTER: Ko KI 

PROVIDER: S-EPMC6804629 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature