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. Author manuscript; available in PMC: 2015 Mar 26.
Published in final edited form as: Nat Rev Rheumatol. 2014 Sep 30;11(1):35–44. doi: 10.1038/nrrheum.2014.162

Figure 2. Functions of AMPK and SIRT1 in chondrocyte resistance to cell stress and inflammatory processes that promote matrix catabolism.

Figure 2

AMPK, which has multiple endogenous and exogenous activators, promotes activation of SIRT1. LKB1 is the primary upstream kinase that promotes AMPK activity, and decreased LKB1 increases chondrocyte matrix procatabolic responses to IL-1β and TNF. Active LKB1 and AMPK are decreased in OA, injured, and ageing chondrocytes. AMPK and SIRT1 exert anti-inflammatory effects, including inhibition of NFκB activation via SIRT1, which deacetylates the p65 subunit of NFκB and thereby primes p65 for proteasomal degradation; these effects limit chondrocyte matrix procatabolic responses. In addition, AMPK and SIRT1 promote autophagy, with attendant repair of damaged organelles, such as mitochondria and ER, and AMPK and SIRT1 inhibit ER stress, providing further means to limit inflammation in OA cartilage.

Abbreviations: AMPK, 5′-AMP-activated protein kinase; ER, endoplasmic reticulum; LKB1, liver protein kinase B1; SIRT1, NAD-dependent protein deacetylase sirtuin-1.