Metabolic profiling of chondrocyte mechanotransduction under physiological and injurious mechanical stimulation

Abstract

Osteoarthritis (OA) is the leading cause of disability worldwide, affecting over 600 million people. OA is characterized by the progressive degradation of articular cartilage, subchondral bone, and synovium. In 2016, OA was responsible for an estimated $80 billion in healthcare spending in the USA, and the population of patients with doctor-diagnosed OA is expected to reach 1 billion by 2050 [1]. OA progression is increasingly recognized as both a mechanically driven and metabolically regulated disease. Altered cellular responses to load interact with dysregulated metabolic pathways, causing OA progression and an imbalance of matrix synthesis and degradation. Cartilage injury is a major clinical concern because it initiates the onset of post-traumatic Osteoarthritis (PTOA), leading to progressive pain, joint dysfunction, and long-term disability. In summary, the overall goal of this research is to better inform future studies on the role of central metabolism in chondrocyte mechanotransduction. Specifically, the role of physiological and injurious mechanical stimulation on the metabolic profiles of chondrocytes will be examined. By integrating in vitro mechanical testing with targeted metabolomics, this work aims to identify how different mechanical stimuli affect central metabolism in human OA and normal bovine chondrocytes