Chemistry & Biochemistry
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The Department of Chemistry and Biochemistry offers research-oriented programs culminating in the Doctor of Philosophy degree. The faculty in the department have expertise over a broad range of specialty areas including synthesis, structure, spectroscopy, and mechanism. In each of these fields, the strength of the department has been recognized at the international level.
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Item Metabolic Phenotypes Reflect Patient Sex and Injury Status: A Cross-Sectional Analysis of Human Synovial Fluid(Elsevier BV, 2023-09) Welhaven, Hope D.; Welfley, Avery H.; Pershad, Prayag; Satalich, James; O'Connell, Robert; Bothner, Brian; Vap, Alexander R.; June, Ronald K.Objective. Osteoarthritis is a heterogeneous disease. The objective was to compare differences in underlying cellular mechanisms and endogenous repair pathways between synovial fluid (SF) from male and female participants with different injuries to improve the current understanding of the pathophysiology of downstream post-traumatic osteoarthritis (PTOA). Design. SF from n = 33 knee arthroscopy patients between 18 and 70 years with no prior knee injuries was obtained pre-procedure and injury pathology assigned post-procedure. SF was extracted and analyzed via liquid chromatography-mass spectrometry metabolomic profiling to examine differences in metabolism between injury pathologies (ligament, meniscal, and combined ligament and meniscal) and patient sex. Samples were pooled and underwent secondary fragmentation to identify metabolites. Results. Different knee injuries uniquely altered SF metabolites and downstream pathways including amino acid, lipid, and inflammatory-associated metabolic pathways. Notably, sexual dimorphic metabolic phenotypes were examined between males and females and within injury pathology. Cervonyl carnitine and other identified metabolites differed in concentrations between sexes. Conclusions. These results suggest that different injuries and patient sex are associated with distinct metabolic phenotypes. Considering these phenotypic associations, a greater understanding of metabolic mechanisms associated with specific injuries, sex, and PTOA development may yield data regarding how endogenous repair pathways differ between male and female injury types. Ongoing metabolomic analysis of SF in injured male and female patients can be performed to monitor PTOA development and progression.Item 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.Item Effects of mechanical stimulation on metabolomic profiles of SW1353 chondrocytes: shear and compression(The Company of Biologists, 2022-01) Welhaven, Hope D.; McCutchen, Carley N.; June, Ronald K.Mechanotransduction is a biological phenomenon where mechanical stimuli are converted to biochemical responses. A model system for studying mechanotransduction are the chondrocytes of articular cartilage. Breakdown of this tissue results in decreased mobility, increased pain, and reduced quality of life. Either disuse or overloading can disrupt cartilage homeostasis, but physiological cyclical loading promotes cartilage homeostasis. To model this, we exposed SW1353 cells to cyclical mechanical stimuli, shear and compression, for different durations of time (15 and 30 min). By utilizing liquid chromatography-mass spectroscopy (LC-MS), metabolomic profiles were generated detailing metabolite features and biological pathways that are altered in response to mechanical stimulation. In total, 1457 metabolite features were detected. Statistical analyses identified several pathways of interest. Taken together, differences between experimental groups were associated with inflammatory pathways, lipid metabolism, beta-oxidation, central energy metabolism, and amino acid production. These findings expand our understanding of chondrocyte mechanotransduction under varying loading conditions and time periods. This article has an associated First Person interview with the first author of the paper.Item Characterization of synovial fluid metabolomic phenotypes of cartilage morphological changes associated with osteoarthritis(2019-08) Carlson, Alyssa K.; Rawle, Rachel A.; Wallace, Cameron W.; Brooks, Ellen G.; Adams, Erik; Greenwood, Mark C.; Olmer, Merissa; Lotz, Martin K.; Bothner, Brian; June, Ronald K."Objective Osteoarthritis (OA) is a multifactorial disease with etiological heterogeneity. The objective of this study was to classify OA subgroups by generating metabolomic phenotypes from human synovial fluid. Design: Post mortem synovial fluids (n = 75) were analyzed by high performance-liquid chromatography mass spectrometry (LC-MS) to measure changes in the global metabolome. Comparisons of healthy (grade 0), early OA (grades I-II), and late OA (grades III-IV) donor populations were considered to reveal phenotypes throughout disease progression. Results: Global metabolomic profiles in synovial fluid were distinct between healthy, early OA, and late OA donors. Pathways differentially activated among these groups included structural deterioration, glycerophospholipid metabolism, inflammation, central energy metabolism, oxidative stress, and vitamin metabolism. Within disease states (early and late OA), subgroups of donors revealed distinct phenotypes. Synovial fluid metabolomic phenotypes exhibited increased inflammation (early and late OA), oxidative stress (late OA), or structural deterioration (early and late OA) in the synovial fluid. Conclusion: These results revealed distinct metabolic phenotypes in human synovial fluid, provide insight into pathogenesis, represent novel biomarkers, and can move toward developing personalized interventions for subgroups of OA patients.