Synthetic gene circuits for preventing disruption of the circadian clock due to interleukin-1-induced inflammation

Lara Pferdehirt, Anna R. Damato, Michal Dudek, Qing Jun Meng, Erik D. Herzog, Farshid Guilak

Research output: Contribution to journalArticlepeer-review

Abstract

The circadian clock regulates tissue homeostasis through temporal control of tissue-specific clock-controlled genes. In articular cartilage, disruptions in the circadian clock are linked to a procatabolic state. In the presence of inflammation, the cartilage circadian clock is disrupted, which further contributes to the pathogenesis of diseases such as osteoarthritis. Using synthetic biology and tissue engineering, we developed and tested genetically engineered cartilage from murine induced pluripotent stem cells (miPSCs) capable of preserving the circadian clock in the presence of inflammation. We found that circadian rhythms arise following chondrogenic differentiation of miPSCs. Exposure of tissue-engineered cartilage to the inflammatory cytokine interleukin-1 (IL-1) disrupted circadian rhythms and degraded the cartilage matrix. All three inflammation-resistant approaches showed protection against IL-1-induced degradation and loss of circadian rhythms. These synthetic gene circuits reveal a unique approach to support daily rhythms in cartilage and provide a strategy for creating cell-based therapies to preserve the circadian clock.

Original languageEnglish
Pages (from-to)eabj8892
JournalScience Advances
Volume8
Issue number21
DOIs
StatePublished - May 27 2022

Fingerprint

Dive into the research topics of 'Synthetic gene circuits for preventing disruption of the circadian clock due to interleukin-1-induced inflammation'. Together they form a unique fingerprint.

Cite this