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. Howeve...
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| Format: | Journal article |
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Nature Publishing Group
2018
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| _version_ | 1797104515592224768 |
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| author | Sacitharan, P Lwin, S Gharios, G Edwards, JR |
| author_facet | Sacitharan, P Lwin, S Gharios, G Edwards, JR |
| author_sort | Sacitharan, P |
| collection | OXFORD |
| description | 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 autophagyrelated 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. |
| first_indexed | 2024-03-07T06:34:50Z |
| format | Journal article |
| id | oxford-uuid:f73c04d0-051f-489b-866a-bf524b284f0d |
| institution | University of Oxford |
| last_indexed | 2024-03-07T06:34:50Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | oxford-uuid:f73c04d0-051f-489b-866a-bf524b284f0d2022-03-27T12:41:23ZSpermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f73c04d0-051f-489b-866a-bf524b284f0dSymplectic Elements at OxfordNature Publishing Group2018Sacitharan, PLwin, SGharios, GEdwards, JRAgeing 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 autophagyrelated 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. |
| spellingShingle | Sacitharan, P Lwin, S Gharios, G Edwards, JR Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300 |
| title | Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300 |
| title_full | Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300 |
| title_fullStr | Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300 |
| title_full_unstemmed | Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300 |
| title_short | Spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via EP300 |
| title_sort | spermidine restores dysregulated autophagy and polyamine synthesis in aged and osteoarthritic chondrocytes via ep300 |
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