Dehydroepiandrosterone: molecular mechanisms and therapeutic implications in osteoarthritis

Publication date: Available online 19 May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Kai Huang, Li-dong Wu
Dehydroepiandrosterone (DHEA), a 19-carbon steroid hormone primarily synthesized in the adrenal gland, exerts a chondroprotective effect against osteoarthritis (OA) and has been considered an effective candidate of disease-modifying OA drugs (DMOADs) that slow disease progression. We and others previously demonstrated that DHEA exerted a beneficial effect on osteoarthritic cartilage by positively modulating the balance between anabolic and catabolic factors (e.g., MMPs/TIMP-1, ADAMTS/TIMP-3 and cysteine proteinases/cystatin C), inhibiting catabolic signaling pathways (e.g., Wnt/β-catenin), and suppressing proinflammatory cytokines-mediated low-grade synovial inflammation (e.g., IL-1β). However, the full picture of the pharmacological molecular mechanism(s) underlying the activity of DHEA against OA is still incomplete, and a comprehensive and up-to-date review article in this field is unavailable. In this review, recent findings (apart from the well documented pathogenesis of OA) regarding disease-related mechanisms involving low grade synovial inflammation, cartilage matrix stiffness, chondrocyte autophagy and the roles of a variety of catabolic cellular signaling pathways are discussed. Moreover, the possible relationship between these disease-related mechanisms and DHEA action is discussed. Emerging evidence from in vivo and in vitro studies were scrutinized and are concisely presented to demonstrate the investigational and putative mechanisms underlying the anti-OA potential of DHEA.

Graphical abstract

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