Aggrecan
Aggrecan is the large proteoglycan of cartilage, a protein core carrying many sugar chains that draw in water and let cartilage resist compression. It sits within the type II collagen network.
Also called aggregating proteoglycan, ACAN (its gene).
Its sugar chains, chondroitin sulphate and keratan sulphate, carry negative charges that hold water in the tissue. That trapped water is central to how cartilage takes load: the high resistance to water flowing through the matrix, and the pressure of the water within it, carry much of the force (Sophia Fox 2009).
Aggrecan is a common marker of how well chondrocytes are keeping up their matrix. Alpha-lipoic acid raised aggrecan gene activity in a rat model of osteoarthritis (Wang 2016); dihydrolipoic acid lessened the fall in aggrecan in mouse cartilage cells exposed to an inflammatory signal (Chen 2026); and switching on Nrf2 increased aggrecan gene expression in human osteoarthritic cartilage cells (Taylor 2023).
ADAMTS5, an enzyme that cuts aggrecan, rose alongside MMP13 when human cartilage cells were exposed to hydrogen peroxide, an inflammatory signal or calcium crystals (Rong 2019).
Sources
- Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: structure, composition, and function. Sports Health 2009.
- Wang J, Sun H, Fu Z et al. Chondroprotective effects of alpha-lipoic acid in a rat model of osteoarthritis. Free Radic Res 2016.
- Chen Y, Fang J, Zhou Z et al. Dihydrolipoic acid suppresses ferroptosis in chondrocytes to ameliorate the progression of osteoarthritis by modulating the FOXO1/TXNIP signaling pathway. Free Radic Biol Med 2026.
- Taylor EL, Collins JA, Gopalakrishnan P et al. Age and oxidative stress regulate Nrf2 homeostasis in human articular chondrocytes. Osteoarthritis Cartilage 2023.
- Rong J, Zhu M, Munro J et al. Altered expression of the core circadian clock component PERIOD2 contributes to osteoarthritis-like changes in chondrocyte activity. Chronobiol Int 2019.
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