Modulation of TRPV4 protects against degeneration induced by sustained loading and promotes matrix synthesis in the intervertebral disc

Autor: Garrett W. D. Easson, Alireza Savadipour, Akila Anandarajah, Leanne E. Iannucci, Spencer P. Lake, Farshid Guilak, Simon Y. Tang
Rok vydání: 2022
Předmět:
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 37(2)
ISSN: 1530-6860
Popis: While it is well known that mechanical signals can either promote or disrupt intervertebral disc (IVD) homeostasis, the molecular mechanisms for transducing mechanical stimuli are not fully understood. The transient receptor potential vanilloid 4 (TRPV4) ion channel activated in isolated IVD cells initiates extracellular matrix (ECM) gene expression, while TRPV4 ablation reduces cytokine production in response to circumferential stretching. However, the role of TRPV4 on ECM maintenance during tissue-level mechanical loading remains unknown. Using an organ culture model, we modulated TRPV4 function over both short- (hours) and long-term (days) and evaluated the IVDs' response. Activating TRPV4 with the agonist GSK101 resulted in a Ca
Databáze: OpenAIRE