Molecular mechanisms of mechanical load-induced osteoarthritis

Abstract

Introduction Mechanical loading enhances the progression of osteoarthritis. However, its molecular mechanisms have not been established. Objective The aim of this review was to summarize the probable mechanisms of mechanical load-induced osteoarthritis. Methods A comprehensive search strategy was used to search PubMed and EMBASE databases (from the 15th of January 2015 to the 20th of October 2020). Search terms included “osteoarthritis”, “mechanical load”, and “mechanism”. Results Abnormal mechanical loading activates the interleukin-1β, tumour necrosis factor-α, nuclear factor kappa-B, Wnt, transforming growth factor-β, microRNAs pathways, and the oxidative stress pathway. These pathways induce the pathological progression of osteoarthritis. Mechanical stress signal receptors such as integrin, ion channel receptors, hydrogen peroxide-inducible clone-5, Gremlin-1, and transient receptor potential channel 4 are present in the articular cartilages. Conclusion This review highlights the molecular mechanisms of mechanical loading in inducing chondrocyte apoptosis and extracellular matrix degradation. These mechanisms provide potential targets for osteoarthritis prevention and treatment.

Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

“…Consistently, miR-137 is also reported to decrease inflammation, oxidative stress, neuronal injury, and cognitive impairment in mice with ischemic stroke (Tian et al, 2020). Similarly, a study reports that miR-27a mimics can suppress oxygen glucose deprivation (OGD)-induced oxidative injury in HT22 cells (Li et al, 2021). Both miR-137 and miR-27a exhibits protective activities against oxidative stress.…”

“…Many studies have demonstrated that bulk RNA sequencing and single-cell sequencing data have been used for the analysis in the pathological development of OA (Li et al, 2021). LncRNA LINC00917 and CTD-2246P4.1 have been reported to regulate angiogenesis in OA cartilage by mediating SPHK1 (Chen et al, 2015), which is associated with angiogenesis and promotes the survival of endothelial cells, the processes of cartilage degradation, and the development of OA (Minashima et al, 2014).…”

“…Osteoarthritis (OA) is histopathologically marked by progressive degradation of extracellular matrix (ECM) in joint articular cartilage. Mechanical stimulation, implicated in articular cartilage development and maintenance, is dynamic, and it is supposed to support the synthesis of extracellular matrix (ECM) under normal mechanical loading and inhibit the production of ECM under persistent improper loading ( Fang et al, 2021 ). Many studies have reported that exercise affects the physiological actions of a joint in a mechanical intensity-dependent manner.…”

Mechanistic Insight Into the Roles of Integrins in Osteoarthritis

“…Conversely, excessive mechanical load alters cartilage composition and causes focal degeneration of cartilage, leading to disease (Smith et al, 2004;Monfort et al, 2006). Excessive mechanical load acting as signals from the ECM can activate integrins, which further promotes the progressive destruction of the cartilage matrix in OA (Fang et al, 2021). Under excessive mechanical load, integrins can regulate the responses of chondrocytes to mechanical stimulation through multiple pathways.…”

Bardoxolone-Methyl Prevents Oxidative Stress-Mediated Apoptosis and Extracellular Matrix Degradation in vitro and Alleviates Osteoarthritis in vivo

“…Increasing evidence has shown that chondrocyte apoptosis serves an important role in OA. [3][4][5] Multiple pathological factors including inflammatory cytokines, mechanical stress leads to excessive reactive oxygen species (ROS) production. High concentrations of ROS triggers intracellular oxidative stress and thus promote cell apoptosis.…”