{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:03:47Z","timestamp":1777478627507,"version":"3.51.4"},"reference-count":41,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["CARTILAGE"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cartilage degeneration is a key feature of osteoarthritis (OA) and rheumatoid arthritis and is thought to negatively impact patients\u2019 quality of life. Diclofenac etalhyaluronate (DEH, SI-613\/ONO-5704) is a hyaluronic acid (HA) derivative chemically bound to diclofenac (DF) that has been reported to improve OA symptoms; however, its effect on cartilage degeneration remains unknown. In the present study, we investigated the chondroprotective effect of DEH in rats with collagen-induced arthritis and interleukin-1\u03b2-stimulated human chondrocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Rats with collagen-induced arthritis were administered DEH and HA intra-articularly, and DF orally. Knee joint swelling, histological scores of articular cartilage, and inflammatory (Il1b) and catabolic (Mmp3 and Mmp13) gene expression in the synovial tissue and cartilage were evaluated. In vitro direct effects of DEH on matrix metalloproteinase (MMP)-3 and MMP-13 expression were examined in interleukin-1\u03b2-stimulated human chondrocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In a rat model of collagen-induced arthritis, a single intra-articular dose of DEH inhibited knee joint inflammation and cartilage degeneration. Daily oral administration of DF had similar effects. Conversely, HA administered as a single intra-articular dose had no effect. Only DEH inhibited Mmp3 gene expression in the cartilage, whereas DEH and DF inhibited Mmp3 and Mmp13 mRNA expression in the synovial tissue. In interleukin-1\u03b2-stimulated human chondrocytes, DEH and HA inhibited MMP-3 and MMP-13 production, whereas DF had no effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this study, we demonstrated the chondroprotective effect of DEH in rats with collagen-induced arthritis and in interleukin-1\u03b2-stimulated human chondrocytes. Thus, DEH may suppress cartilage degeneration in patients with musculoskeletal diseases, such as OA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/19476035231224050","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:33:55Z","timestamp":1707179635000},"page":"388-398","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Diclofenac Etalhyaluronate (SI-613\/ONO-5704) on Cartilage Degeneration in Arthritic Rats and Inflammatory Cytokine-Stimulated Human Chondrocytes"],"prefix":"10.1177","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7474-109X","authenticated-orcid":false,"given":"Shuhei","family":"Takada","sequence":"first","affiliation":[{"name":"Central Research Laboratory, Research &amp; Development Division, Seikagaku Corporation, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Risa","family":"Nodera","sequence":"additional","affiliation":[{"name":"Central Research Laboratory, Research &amp; Development Division, Seikagaku Corporation, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiji","family":"Yoshioka","sequence":"additional","affiliation":[{"name":"Central Research Laboratory, Research &amp; Development Division, Seikagaku Corporation, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"e_1_3_2_2_2","article-title":"Articular cartilage and osteoarthritis","volume":"54","author":"Buckwalter JA","year":"2005","unstructured":"Buckwalter JA, Mankin HJ, Grodzinsky AJ. 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