{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:00:12Z","timestamp":1777478412418,"version":"3.51.4"},"reference-count":49,"publisher":"SAGE Publications","issue":"2_suppl","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["MEXT 163007"],"award-info":[{"award-number":["MEXT 163007"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["CARTILAGE"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the role and characterize the molecular mechanisms regulating apoptosis and autophagy in nitric oxide (NO)\u2013induced chondrocyte cell death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Cell apoptosis and autophagy were evaluated in chondrocytes treated with sodium nitroprusside (SNP) combined with the presence or absence of interleukin-1 beta (IL-1\u03b2) and nutrient-deprived conditions. The concentration of nitrite was determined by Griess reaction. Activation of apoptosis and autophagy were determined by immunocytochemistry, Western blot, and quantitative real-time polymerase chain reaction (qPCR) analysis. Flow cytometry and MTT assay were used to assess cell viability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cotreatment of chondrocytes with SNP and IL-1\u03b2 under nutrient-deprived condition potentially enhanced the effect of NO-induced cell death. Immunocytochemistry, Western blot, and qPCR analysis indicated that treatment of chondrocytes with SNP significantly reduced autophagic activity, autophagic flux, and multiple autophagy-related (Atg) genes expression. These findings were associated with an increase in ERK, Akt, and mTOR phosphorylation, whereas autophagy induction through mTOR\/p70S6K inhibition by rapamycin significantly suppressed NO-induced cell apoptosis. Furthermore, the cleavage of poly(ADP-ribose) polymerase (PARP) and caspase-3 activation in response to apoptosis was weakly detected. These results corresponded with a significant increase in apoptosis-inducing factor (AIF) expression, suggesting the involvement of the caspase-independent pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results demonstrate that in chondrocyte cultures with cells induced into an osteoarthritis state, NO inhibits autophagy and induces chondrocyte apoptosis mainly, but not completely through the caspase-independent pathway. Our data suggest that autophagy is a protective mechanism in the pathogenesis of osteoarthritis and could be proposed as a therapeutic target for degenerative joint diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1947603520976768","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T08:49:51Z","timestamp":1607935791000},"page":"826S-838S","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["An Insight into the Role of Apoptosis and Autophagy in Nitric Oxide\u2013Induced Articular Chondrocyte Cell Death"],"prefix":"10.1177","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9745-3115","authenticated-orcid":false,"given":"Ekkapol","family":"Akaraphutiporn","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, 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