Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms11051
Keywords
-
Categories
Funding
- Swiss National Science Foundation [PBELP3-138585, PA00P3-145403, P300P3-151198]
- Japan Society for the Promotion of Science (JSPS) [15H06348]
- Astellas Foundation for Research on Metabolic Disorders
- Takeda Science Foundation
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [26670663, 15H06348] Funding Source: KAKEN
- Swiss National Science Foundation (SNF) [P300P3_151198, PBELP3_138585, PA00P3_145403] Funding Source: Swiss National Science Foundation (SNF)
Ask authors/readers for more resources
Tissue injury and the healing response lead to the release of endogenous danger signals including Toll-like receptor (TLR) and interleukin-1 receptor, type 1 (IL-1R1) ligands, which modulate the immune microenvironment. Because TLRs and IL-1R1 have been shown to influence the repair process of various tissues, we explored their role during bone regeneration, seeking to design regenerative strategies integrating a control of their signalling. Here we show that IL-1R1/MyD88 signalling negatively regulates bone regeneration, in the mouse. Furthermore, IL-1b which is released at the bone injury site, inhibits the regenerative capacities of mesenchymal stem cells (MSCs). Mechanistically, IL-1R1/MyD88 signalling impairs MSC proliferation, migration and differentiation by inhibiting the Akt/GSK-3 beta/beta-catenin pathway. Lastly, as a proof of concept, we engineer a MSC delivery system integrating inhibitors of IL-1R1/MyD88 signalling. Using this strategy, we considerably improve MSC-based bone regeneration in the mouse, demonstrating that this approach may be useful in regenerative medicine applications.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available