Research Paper Volume 13, Issue 10 pp 13421—13429

Systemic NF-κB-mediated inflammation promotes an aging phenotype in skeletal stem/progenitor cells

Exposure to Nfkb1-/- circulation results in increased inflammation in bone marrow compartment. (A) Schematic representation of the parabiosis model in which one mouse shares circulation with another surgically-anatomized mouse. A wild-type mouse parabiosed to another wild-type mouse serves as the control (isochronic pair) and Nfkb1-/- mouse parabiosed to a wild-type mouse serves as the experimental group (heterochronic pair). Parabionts are noted as such wild-type parabiosed to wild-type, WTWT; Nfkb1-/- mouse parabiosed to wild-type, Nfkb1-/-WT; and wild-type parabiosed to Nfkb1-/- mouse, WTNfkb1-/-. Green mice depict Beta-actin GFP mice (C57BL/6-Tg(CAG-EGFP)1Osb/J), brown mice represent wild-type mice. (B) Gating strategy demonstrating that parabiosis led to an insignificant transfer of SSPCs from one animal to the other. (C) After six weeks of shared circulation the bone marrow compartment of WTNfkb1-/- mice displayed higher expression of the inflammatory mediators Tnfa, Il1a and Il1b compared to WTWT controls. Conversely, exposure of WT circulation to the Nfkb1-/- bone marrow did not result in a reduced inflammatory status. (n=3, ns, non-significant, *P  **P ≤ 0.01, *** P ≤ 0.001, **** P ≤ 0.0001).

Figure 1. Exposure to Nfkb1-/- circulation results in increased inflammation in bone marrow compartment. (A) Schematic representation of the parabiosis model in which one mouse shares circulation with another surgically-anatomized mouse. A wild-type mouse parabiosed to another wild-type mouse serves as the control (isochronic pair) and Nfkb1-/- mouse parabiosed to a wild-type mouse serves as the experimental group (heterochronic pair). Parabionts are noted as such wild-type parabiosed to wild-type, WTWT; Nfkb1-/- mouse parabiosed to wild-type, Nfkb1-/-WT; and wild-type parabiosed to Nfkb1-/- mouse, WTNfkb1-/-. Green mice depict Beta-actin GFP mice (C57BL/6-Tg(CAG-EGFP)1Osb/J), brown mice represent wild-type mice. (B) Gating strategy demonstrating that parabiosis led to an insignificant transfer of SSPCs from one animal to the other. (C) After six weeks of shared circulation the bone marrow compartment of WTNfkb1-/- mice displayed higher expression of the inflammatory mediators Tnfa, Il1a and Il1b compared to WTWT controls. Conversely, exposure of WT circulation to the Nfkb1-/- bone marrow did not result in a reduced inflammatory status. (n=3, ns, non-significant, *P < 0.05, **P0.01, *** P0.001, **** P0.0001).