TRPV Channels in Osteoarthritis: A Comprehensive Review

Abstract

Osteoarthritis (OA) is a debilitating joint disorder that affects millions of people worldwide. Despite its prevalence, our understanding of the underlying mechanisms remains incomplete. In recent years, transient receptor potential vanilloid (TRPV) channels have emerged as key players in OA pathogenesis. This review provides an in-depth exploration of the role of the TRPV pathway in OA, encompassing its involvement in pain perception, inflammation, and mechanotransduction. Furthermore, we discuss the latest research findings, potential therapeutic strategies, and future directions in the field, shedding light on the multifaceted nature of TRPV channels in OA.

Keywords: TRPV channels; inflammation; mechanotransduction; osteoarthritis; therapeutic strategies.

Figure 1

The roles of TRPV1 channels in osteoarthritis. (1, 2a, 3a) The release of inflammatory factors activates TRPV1 channels, thereby triggering an increase in neuronal excitability and intensifying the transmission of pain signals. (1, 2b, 3b) The activation of TRPV1 channels could lead to the release of inflammatory mediators, such as hormones and cytokines, contributing to the development and persistence of joint pain and inflammation. Furthermore, thermal stimulation during inflammation enhances TRPV1 sensitivity in the pain pathway. Created by Figdraw.com (https://www.figdraw.com).

Figure 2

Mechanisms of TRPV4 channels in osteoarthritis. Inflammatory factors such as IL-1β and TNF-α can promote TRPV4 channel opening; this causes a large influx of Ca²⁺ into the cell. Activation of TRPV4 channels promotes the expressions of Sox9, ACAN, and COL-II through the Ca²⁺/calmodulin (CaM) signaling pathway; this promotes chondrocyte formation and differentiation. However, the activation of TRPV4 channels leads to the release of inflammatory mediators (MMPs, IL-1β, IL-6, and TNF-α), contributing to the development and persistence of joint pain and inflammation. Created by Figdraw.com (https://www.figdraw.com).