Abstract The mechanism by which chondrocytes respond to reduced mechanical loading environments and the subsequent risk of developing osteoarthritis remains unclear. This is of particular concern for astronauts. In space the reduced joint loading forces during prolonged microgravity (10 −6 g) exposure could lead to osteoarthritis (OA), compromising quality of life post-spaceflight. In this study, we encapsulated human chondrocytes in an agarose gel of similar stiffness to the pericellular matrix to mimic the cartilage microenvironment. We then exposed agarose-chondrocyte constructs to simulated microgravity (SM) for four days using a rotating wall vessel (RWV) bioreactor to better assess the cartilage health risks associated with spaceflight. Metabolites extracted from media and agarose gel constructs were analyzed on liquid chromatography-mass spectrometry. Global metabolomic profiling detected a total of 1205 metabolite features, with 497 significant metabolite features identified by ANOVA (FDR-corrected p -value &lt; 0.05). Specific metabolic shifts detected in response to SM exposure resulted in clusters of co-regulated metabolites, with glutathione, nitrogen, histidine, vitamin B 3 , and aminosugars metabolism identified by variable importance in projection scores. Microgravity-induced metabolic shifts in gel constructs and media were indicative of protein synthesis, energy and nucleotide metabolism, and oxidative catabolism. Microgravity associated-metabolic shifts were consistent with our previously published early osteoarthritic metabolomic profiles in human synovial fluid, suggesting that even short-term exposure to microgravity (or other reduced mechanical loading environments) may lead to the development of OA. This work further suggests the potential to detect these metabolic perturbations in synovial fluid in vivo to ascertain osteoarthritis risk in astronauts.

Annika R. Bergstrom

Matthew G. Glimm

Eden A. Houske

Gwendolyn Cooper

Ethan Viles

Marrin Chapman

Katherine Bourekis

Hope D. Welhaven

Priyanka P. Brahmachary

Alyssa K. Hahn

Ronald K. June

Annals of Biomedical Engineering

ANNALS OF BIOMEDICAL ENGINEERING是生物医学工程学会的官方期刊，发表生物工程和生物医学工程主要领域的原创文章。 《年鉴》是一本跨学科的国际期刊，旨在突出解决生物和生物医学问题的综合方法。

The Annals of Biomedical Engineering is the official journal of the Biomedical Engineering Society, dedicated to publishing original research articles in the fields of bioengineering and biomedical engineering. This interdisciplinary international journal aims to highlight integrated approaches to solving biological and biomedical problems.

《Annals of Biomedical Engineering》是生物医学工程学会的官方期刊，专注于发表生物工程和生物医学工程领域的原创研究文章。这本跨学科的国际期刊旨在强调解决生物和生物医学问题的综合方法。

Category	Quartile
医学	2
医学, 工程生物医学	3

Metabolic Profiles of Encapsulated Chondrocytes Exposed to Short-Term Simulated Microgravity

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