In vivo mechanotransduction: Effect of acute exercise on the metabolomic profiles of mouse synovial fluid

Alyssa K Hahn; Rachel A Rawle; Brian Bothner; Erika Barboza Prado Lopes; Timothy M Griffin; Ronald K June

doi:10.1016/j.ocarto.2021.100228

In vivo mechanotransduction: Effect of acute exercise on the metabolomic profiles of mouse synovial fluid

Osteoarthr Cartil Open. 2021 Dec 8;4(1):100228. doi: 10.1016/j.ocarto.2021.100228. eCollection 2022 Mar.

Authors

Alyssa K Hahn^{1

2

3}, Rachel A Rawle^{1

4}, Brian Bothner⁴, Erika Barboza Prado Lopes⁵, Timothy M Griffin^{5

6}, Ronald K June^{2

7}

Affiliations

¹ Molecular Biosciences Program, Montana State University, Bozeman, MT, 59717, USA.
² Department of Cell Biology & Neuroscience, Montana State University, Bozeman, MT, 59717, USA.
³ Department of Biological and Environmental Sciences, Carroll College, Helena, MT, 59625, USA.
⁴ Department of Chemistry & Biochemistry, Montana State University, Bozeman, MT, 59717, USA.
⁵ Aging and Metabolism Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, 73104, USA.
⁶ Veterans Affairs Medical Center, Oklahoma City, OK, 73104, USA.
⁷ Department of Mechanical & Industrial Engineering, Montana State University, Bozeman, MT, 59717, USA.

Abstract

Objective: Exercise is known to induce beneficial effects in synovial joints. However, the mechanisms underlying these are unclear. Synovial joints experience repeated mechanical loading during exercise. These mechanical stimuli are transduced into biological responses through cellular mechanotransduction. Mechanotransduction in synovial joints is typically studied in tissues. However, synovial fluid directly contacts all components of the joint, and thus may produce a whole-joint picture of the mechanotransduction response to loading. The objective of this study was to determine if metabolic phenotypes are present in the synovial fluid after acute exercise as a first step to understanding the beneficial effects of exercise on the joint.

Material and methods: Mice underwent a single night of voluntary wheel running or standard housing and synovial fluid was harvested for global metabolomic profiling by LC-MS. Hierarchical unsupervised clustering, partial least squares discriminant, and pathway analysis provided insight into exercise-induced mechanotransduction.

Results: Acute exercise produced a distinct metabolic phenotype in synovial fluid. Mechanosensitive metabolites included coenzyme A derivatives, prostaglandin derivatives, phospholipid species, tryptophan, methionine, vitamin D3, fatty acids, and thiocholesterol. Enrichment analysis identified several pathways previously linked to exercise including amino acid metabolism, inflammatory pathways, citrulline-nitric oxide cycle, catecholamine biosynthesis, ubiquinol biosynthesis, and phospholipid metabolism.

Conclusion: To our knowledge, this is the first study to investigate metabolomic profiles of synovial fluid during in vivo mechanotransduction. These profiles indicate that exercise induced stress-response processes including both pro- and anti-inflammatory pathways. Further research will expand these results and define the relationship between the synovial fluid and the serum.

Abstract

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