{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T05:58:42Z","timestamp":1767851922160,"version":"3.49.0"},"reference-count":75,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T00:00:00Z","timestamp":1493856000000},"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":["81371706"],"award-info":[{"award-number":["81371706"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81502333"],"award-info":[{"award-number":["81502333"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2016M591437"],"award-info":[{"award-number":["2016M591437"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Slow growth and rapid loss of chondrogenic phenotypes are the major problems affecting chronic cartilage lesions. The role of microRNA-195 (miR-195) and its detailed working mechanism in the fore-mentioned process remains unknown. Fibroblastic growth factor 18 (FGF-18) plays a key role in cartilage homeostasis; whether miR-195 could regulate FGF-18 and its downstream signal pathway in chondrocyte proliferation and maintenance of chondrogenic phenotypes still remains unclear. The present research shows elevated miR-195 but depressed FGF-18 expressed in joint fluid specimens of 20 patients with chronic cartilage lesions and in CH1M and CH3M chondrocytes when compared with that in joint fluid specimens without cartilage lesions and in CH1W and CH2W chondrocytes, respectively. The following loss of function test revealed that downregulation of miR-195 by transfection of miR-195 inhibitors promoted chondrocyte proliferation and expression of a type II collagen \u03b1 I chain (Col2a1)\/aggrecan. Through the online informatics analysis we theoretically predicted that miR-195 could bind to a FGF-18 3\u2032 untranslated region (3\u2032UTR), also, we verified that a miR-195 could regulate the FGF-18 and its downstream pathway. The constructed dual luciferase assay further confirmed that FGF-18 was a direct target of miR-195. The executed anti-sense experiment displayed that miR-195 could regulate chondrocyte proliferation and Col2a1\/aggrecan expression via the FGF-18 pathway. Finally, through an in vivo anterior cruciate ligament transection (ACLT) model, downregulation of miR-195 presented a significantly protective effect on chronic cartilage lesions. Evaluating all of the outcomes of the current research revealed that a decrease of miR-195 protected chronic cartilage lesions by promoting chondrocyte proliferation and maintenance of chondrogenic phenotypes via the targeting of the FGF-18 pathway and that the miR-195\/FGF-18 axis could be a potential target in the treatment of cartilage lesions.<\/jats:p>","DOI":"10.3390\/ijms18050975","type":"journal-article","created":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T11:44:18Z","timestamp":1493898258000},"page":"975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Decrease of miR-195 Promotes Chondrocytes Proliferation and Maintenance of Chondrogenic Phenotype via Targeting FGF-18 Pathway"],"prefix":"10.3390","volume":"18","author":[{"given":"Yong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Joint Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China"},{"name":"The 4th Department of Orthopedic Surgery, The Central Hospital Affiliated to Shenyang Medical College, Shenyang 110024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yadong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"The 4th Department of Orthopedic Surgery, The Central Hospital Affiliated to Shenyang Medical College, Shenyang 110024, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1055\/s-0030-1247771","article-title":"Knee articular cartilage injuries in the National Football League: Epidemiology and treatment approach by team physicians","volume":"22","author":"Brophy","year":"2009","journal-title":"J. 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