Fibronectin Sensitizes Activation of Contractility, YAP, and NF-κB in Nucleus Pulposus Cells.

Intervertebral disc degeneration involves breakdown of the discs of the spine due to genetics, ageing, or faulty mechanical loading. As part of the progression of the disease, nucleus pulposus cells lose their phenotypic characteristics, inducing inflammation and extracellular matrix alterations that result in a loss of disc mechanical homeostasis. Fibronectin is one extracellular matrix molecule that has been shown to be upregulated in disc degeneration and plays an important role in the progression of a wide variety of fibrotic diseases. Fragments of fibronectin have also long been associated with both osteoarthritis and disc degeneration. The goal of this work was to test the effects of fibronectin on disc cell phenotype, mechanosensing, and inflammatory signaling. We identify that fibronectin increases the activation of cellular contractility, the mechanosensitive transcription factor YAP, and the inflammatory transcription factor NF-κB. This results in decreased production and expression of proteoglycans, which are required to maintain healthy disc function. Thus, fibronectin is a potential regulator of phenotypic changes in disc degeneration, and potential target for treating disc degeneration at the cellular level. Understanding the role of fibronectin, and its potential as a therapeutic target, could provide new approaches for preventing or reversing disc degeneration. This article is protected by copyright. All rights reserved.