{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:54:22Z","timestamp":1761710062885,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673112","81972980","82273753","2021JCW-08"],"award-info":[{"award-number":["81673112","81972980","82273753","2021JCW-08"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Basic Research Plan in Shaanxi Province of China","award":["81673112","81972980","82273753","2021JCW-08"],"award-info":[{"award-number":["81673112","81972980","82273753","2021JCW-08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Objective: Kashin-Beck disease (KBD) is a kind of endemic and chronic osteochondropathy in China. This study aims to explore the functional relevance and potential mechanism of Wnt-inducible signaling pathway protein 1 (WISP1) in the pathogenesis of KBD. Design: KBD and control cartilage specimens were collected for tissue section observation and primary chondrocyte culture. Firstly, the morphological and histopathological observations were made under a light and electron microscope. Then, the expression levels of WISP1 as well as molecular markers related to the autophagy pathway and extracellular matrix (ECM) synthesis were detected in KBD and control chondrocytes by qRT-PCR, Western blot, and immunohistochemistry. Furthermore, the lentiviral transfection technique was applied to make a WISP1 knockdown cell model based on KBD chondrocytes. In vitro intervention experiments were conducted on the C28\/I2 human chondrocyte cell line using human recombinant WISP1 (rWISP1). Results: The results showed that the autolysosome appeared in the KBD chondrocytes. The expression of WISP1 was significantly higher in KBD chondrocytes. Additionally, T-2 toxin, a risk factor for KBD onset, could up-regulate the expression of WISP1 in C28\/I2. The autophagy markers ATG4C and LC3II were upregulated after the low-concentration treatment of T-2 toxin and downregulated after the high-concentration treatment. After knocking down WISP1 expression in KBD chondrocytes, MAP1LC3B decreased while ATG4C and COL2A1 increased. Moreover, the rWISP1 protein treatment in C28\/I2 chondrocytes could upregulate the expression of ATG4C and LC3II at the beginning and downregulate them then. Conclusions: Our study suggested that WISP1 might play a role in the pathogenesis of KBD through autophagy.<\/jats:p>","DOI":"10.3390\/ijms242216037","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T11:23:39Z","timestamp":1699356219000},"page":"16037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["WISP1 Is Involved in the Pathogenesis of Kashin-Beck Disease via the Autophagy Pathway"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0047-376X","authenticated-orcid":false,"given":"Ping","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bolun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Yao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, Xi\u2019an Honghui Hospital, Health Science Center, Xi\u2019an Jiaotong University, Xi\u2019an 710054, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0527-9250","authenticated-orcid":false,"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqiang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Qi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chujun","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomeng","family":"Chu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Ye","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiquan","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumeng","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiong","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5317-4387","authenticated-orcid":false,"given":"Yan","family":"Wen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic Disease of National Health Commission of the People\u2019s Republic of China, School of Public Health, Health Science Center, Xi\u2019an Jiaotong University, No. 76 Yanta West Road, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.joca.2014.07.023","article-title":"Recent advances in the research of an endemic osteochondropathy in China: Kashin-Beck disease","volume":"22","author":"Guo","year":"2014","journal-title":"Osteoarthr. 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