Browsing by Author "Griffin, Timothy M."

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Emerging role of metabolic signaling in synovial joint remodeling and osteoarthritis
(2016-12) June, Ronald K.; Liu-Bryan, Ru; Long, Fanxing; Griffin, Timothy M.
Obesity and associated metabolic diseases collectively referred to as the metabolic syndrome increase the risk of skeletal and synovial joint diseases, including osteoarthritis (OA). The relationship between obesity and musculoskeletal diseases is complex, involving biomechanical, dietary, genetic, inflammatory, and metabolic factors. Recent findings illustrate how changes in cellular metabolism and metabolic signaling pathways alter skeletal development, remodeling, and homeostasis, especially in response to biomechanical and inflammatory stressors. Consequently, a better understanding of the energy metabolism of diarthrodial joint cells and tissues, including bone, cartilage, and synovium, may lead to new strategies to treat or prevent synovial joint diseases such as OA. This rationale was the basis of a workshop presented at the 2016 Annual ORS Meeting in Orlando, FL on the emerging role of metabolic signaling in synovial joint remodeling and OA. The topics we covered included (i) the relationship between metabolic syndrome and OA in clinical and pre-clinical studies; (ii) the effect of biomechanical loading on chondrocyte metabolism; (iii) the effect of Wnt signaling on osteoblast carbohydrate and amino acid metabolism with respect to bone anabolism; and (iv) the role of AMP-activated protein kinase in chondrocyte energetic and biomechanical stress responses in the context of cartilage injury, aging, and OA. Although challenges exist for measuring in vivo changes in synovial joint tissue metabolism, the findings presented herein provide multiple lines of evidence to support a central role for disrupted cellular energy metabolism in the pathogenesis of OA.
In vivo mechanotransduction: Effect of acute exercise on the metabolomic profiles of mouse synovial fluid
(Elsevier BV, 2022-03) Hahn, Alyssa K.; Rawle, Rachel A.; Bothner, Brian; Prado Lopes, Erika Barboza; Griffin, Timothy M.; June, Ronald K.
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.