Journal
OSTEOARTHRITIS AND CARTILAGE
Volume 23, Issue 11, Pages 1835-1842Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.joca.2014.12.016
Keywords
Inflammation; Energy metabolism; Cartilage homeostasis; AMPK; SIRT1
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Funding
- U.S. Department of Veterans Affairs grant [1I01BX002234]
- National Institutes of Health grant [AR1067966]
- Innovative Science Grant from the Arthritis Foundation [6045]
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Articular cartilage degeneration is hallmark of osteoarthritis (OA). Low-grade chronic inflammation in the joint can promote OA progression. Emerging evidence indicates that bioenergy sensors couple metabolism with inflammation to switch physiological and clinical phenotypes. Changes in cellular bioenergy metabolism can reprogram inflammatory responses, and inflammation can disturb cellular energy balance and increase cell stress. AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) are two critical bioenergy sensors that regulate energy balance at both cellular and whole-body levels. Dysregulation of AMPK and SIRT1 has been implicated in diverse human diseases and aging. This review reveals recent findings on the role of AMPK and SIRT1 in joint tissue homeostasis and OA, with a focus on how AMPK and SIRT1 in articular chondrocytes modulate intracellular energy metabolism during stress responses (e.g., inflammatory responses) and how these changes dictate specific effector functions, and discusses translational significance of AMPK and SIRT1 as new therapeutic targets for OA. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
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