Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300

Ageing is the primary risk factor for osteoarthritis (OA). A decline in the ageing-associated process of autophagy is suggested as a potential contributor to OA development. Polyamines such as spermidine decrease during ageing, contributing to impaired autophagy and reduced cellular function. However, the role of polyamines and their effect on the regulatory mechanism governing autophagy in aged and arthritic cartilage tissue has not been established. Elucidating if polyamine regulation of autophagy is impaired during ageing and OA in chondrocytes may lead to improved treatment approaches to protect against cartilage degradation. Our results indicate that polyamine synthesis was decreased in aged and OA cartilage, along with reduced autophagy activity, evidenced by decreased autophagy-related gene and protein expression and autophagosome formation. Importantly, spermidine treatment increased the expression of the acetyltransferase EP300, which binds to crucial autophagy proteins, Beclin1 and LC3, and elevates chondrocyte autophagy. Our data indicate spermidine prevents the ageing- and OA-related decrease in autophagy and may protect against OA development. Aging: toward a natural treatment for osteoarthritis The naturally occurring small molecule spermidine might prevent and repair the cartilage damage in osteoarthritis, commonly associated with aging. Spermidine was first found in semen but is widely distributed in animals and plants and is known to promote longevity in mammals. During normal aging, a process of “autophagy” in which cells degrade and recycle used materials is known to decline in chrondrocytes, cells which produce and maintain cartilage. Researchers in the UK led by James Edwards at the University of Oxford have uncovered details of the biochemical mechanisms linking spermidine and autophagy. Treating cultured human and mouse chrondrocytes with spermidine can reverse the decline in autophagy. The researchers identified specific genes and proteins involved in spermidine’s effects. Spermidine treatment might restore normal autophagy, combatting osteoarthritis.