{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:07:54Z","timestamp":1791479274044,"version":"4.3.4"},"reference-count":59,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Innovation System & Education (RISE) program through the Chungbuk Regional Innovation System & Education Center"},{"name":"Ministry of Education (MOE) and the Chungcheonbuk-do","award":["2025-RISE-11-014-03"],"award-info":[{"award-number":["2025-RISE-11-014-03"]}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2025-02273102"],"award-info":[{"award-number":["RS-2025-02273102"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korean government"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Osteoarthritis (OA) is a pervasive chronic joint disease characterized by the triad of persistent articular cartilage degeneration, debilitating synovial inflammation, and sustained chronic pain. Although salmon nasal cartilage proteoglycan (SPG) is recognized for supporting joint health, the precise molecular mechanism underlying its effects during OA progression remains to be fully elucidated. This study evaluated the therapeutic efficacy of SPG using a monosodium iodoacetate (MIA)-induced mouse model. Methods: A total of 180 male C57BL\/6J mice (six-week-old) were utilized, organized into three independent cohorts to analyze distinct analytical endpoints: (1) pain assessment, histology, and immunohistochemistry; (2) mRNA expression analysis for early-stage OA (Day 3); and (3) mRNA expression analysis for the late-stage OA (Day 28). All subjects received daily oral treatment via gavage, commencing 5 days prior to OA induction and continuing until the designated experimental termination points (either Day 3 or Day 28). Each cohort comprised five experimental groups (n = 10\u201312 per group): a saline-injected Sham group, an MIA-induced Control group, a positive comparator receiving celecoxib (CLX, 20 mg\/kg\/day), and two groups administered SPG at a dose of 50 or 100 mg\/kg\/day. Results: Our findings demonstrated that SPG, particularly at the 100 mg\/kg dose, significantly mitigated joint pain symptoms, performing comparably to CLX. Histopathological assessments confirmed that SPG effectively preserved the structural integrity of the cartilage matrix and substantially reduced pathological damage, as evidenced by lower Mankin scores. Mechanistically, SPG treatment led to a marked downregulation of degradative enzymes, including matrix metalloproteinase-3 (MMP-3) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), while concurrently normalizing the levels of tissue inhibitors of metalloproteinases (TIMPs). Furthermore, SPG prevented the aberrant, over-compensatory expression of anabolic markers such as SRY-box transcription factor 9 (SOX-9), type II collagen alpha 1 chain (COL2A1), and aggrecan (ACAN) typically observed in the disease\u2019s later stages. While SPG demonstrated a limited impact on broadly pro-inflammatory cytokine profiles, it specifically and significantly reduced interleukin-6 (IL-6) gene expression during the chronic phase. Conclusions: These results suggest that SPG serves as a promising natural agent that maintains articular homeostasis by balancing matrix metabolic pathways, positioning it as a scientifically validated functional food candidate for the management of joint health.<\/jats:p>","DOI":"10.3390\/nu18010176","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:28:57Z","timestamp":1767626937000},"page":"176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Salmon Nasal Cartilage Proteoglycan Ameliorate Joint Pain and Cartilage Degradation by Regulating Catabolic and Anabolic Homeostasis in MIA-Induced Osteoarthritis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0970-4878","authenticated-orcid":false,"given":"Min","family":"Yu","sequence":"first","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, 194-21 Osongsaengmyoung 1-ro, Osong-eup, Heungduk-gu, Cheongju 29160, Chungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Eun","family":"Jo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, 194-21 Osongsaengmyoung 1-ro, Osong-eup, Heungduk-gu, Cheongju 29160, Chungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Bae","family":"Son","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, 194-21 Osongsaengmyoung 1-ro, Osong-eup, Heungduk-gu, Cheongju 29160, Chungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, 194-21 Osongsaengmyoung 1-ro, Osong-eup, Heungduk-gu, Cheongju 29160, Chungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngsik","family":"Seo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, 194-21 Osongsaengmyoung 1-ro, Osong-eup, Heungduk-gu, Cheongju 29160, Chungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6656-6523","authenticated-orcid":false,"given":"Sang Bae","family":"Han","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, 194-21 Osongsaengmyoung 1-ro, Osong-eup, Heungduk-gu, Cheongju 29160, Chungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2102-1850","authenticated-orcid":false,"given":"Hyun Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"R&D Center, Naturetech Inc., 450-86 Maebong-ro, Byeongcheon-myeon, Dongnam-gu, Cheonan 31257, Chungnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4747-9844","authenticated-orcid":false,"given":"Seon Gil","family":"Do","sequence":"additional","affiliation":[{"name":"R&D Center, Naturetech Inc., 450-86 Maebong-ro, Byeongcheon-myeon, Dongnam-gu, Cheonan 31257, Chungnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1833-372X","authenticated-orcid":false,"given":"Hanjoong","family":"Jo","sequence":"additional","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, 1760 Haygood Drive NE, Atlanta, GA 30306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7520-6909","authenticated-orcid":false,"given":"Dong Ju","family":"Son","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungbuk National University, 194-21 Osongsaengmyoung 1-ro, Osong-eup, Heungduk-gu, Cheongju 29160, Chungbuk, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"ref_1","first-page":"646","article-title":"Burden of major musculoskeletal conditions","volume":"81","author":"Woolf","year":"2003","journal-title":"Bull. World Health Organ."},{"key":"ref_2","first-page":"3","article-title":"Osteoarthritis is a serious disease","volume":"37","author":"Hawker","year":"2019","journal-title":"Clin. Exp. 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