Dehydroepiandrosterone: Molecular mechanisms and therapeutic implications in osteoarthritis

Publication date: Available online 19 May 2018Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Kai Huang, Li-dong WuAbstractDehydroepiandrosterone (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 a...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research