{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T18:45:22Z","timestamp":1772131522964,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR-109-237"],"award-info":[{"award-number":["DMR-109-237"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2314-B-039-011-; MOST 107-2320-B-039-019-MY3"],"award-info":[{"award-number":["MOST 108-2314-B-039-011-; MOST 107-2320-B-039-019-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The development of osteoarthritis (OA) is characterized by synovial inflammation and the upregulation of vascular cell adhesion molecule type 1 (VCAM-1) in human osteoarthritis synovial fibroblasts (OASFs). This increase in VCAM-1 expression promotes monocyte adhesion to OASFs. The adipokine resistin is known to promote the release of inflammatory cytokines during OA progression. In this study, we identified significantly higher levels of resistin and CD68 (a monocyte surface marker) expression in human OA tissue compared with in healthy control tissue. We also found that resistin enhances VCAM-1 expression in human OASFs and facilitates the adhesion of monocytes to OASFs. These effects were attenuated by inhibitors of PKC\u03b1, p38, and JNK; their respective siRNAs; and by a microRNA-381 (miR-381) mimic. In our anterior cruciate ligament transection (ACLT) rat model of OA, the inhibition of resistin activity prevented ACLT-induced damage to the OA rat cartilage and pathological changes in resistin and monocyte expression. We also found that resistin affects VCAM-1 expression and monocyte adhesion in human OASFs by inhibiting miR-381 synthesis via the PKC\u03b1, p38, and JNK signaling pathways. Our clarification of the crucial role played by resistin in the pathogenesis of OA may lead to more effective therapy that reduces OA inflammation.<\/jats:p>","DOI":"10.3390\/cells9061369","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T09:19:27Z","timestamp":1591089567000},"page":"1369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Resistin Enhances VCAM-1 Expression and Monocyte Adhesion in Human Osteoarthritis Synovial Fibroblasts by Inhibiting MiR-381 Expression through the PKC, p38, and JNK Signaling Pathways"],"prefix":"10.3390","volume":"9","author":[{"given":"Wei-Cheng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan"},{"name":"Division of Sports Medicine &amp; Surgery, Department of Orthopedic Surgery, MacKay Memorial Hospital, Taipei 104, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Yang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2992-4608","authenticated-orcid":false,"given":"Shu-Jui","family":"Kuo","sequence":"additional","affiliation":[{"name":"School of Medicine, China Medical University, Taichung 404, Taiwan"},{"name":"Department of Orthopedic Surgery, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan-Chi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin 651, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung-Chang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan"},{"name":"Division of Sports Medicine &amp; Surgery, Department of Orthopedic Surgery, MacKay Memorial Hospital, Taipei 104, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen-Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7522-6352","authenticated-orcid":false,"given":"Shih-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan"},{"name":"Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-8352","authenticated-orcid":false,"given":"Chih-Hsin","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Medicine, China Medical University, Taichung 404, Taiwan"},{"name":"Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan"},{"name":"Department of Biotechnology, College of Health Science, Asia University, Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4075","DOI":"10.18632\/aging.102038","article-title":"Tgf-beta1 enhances foxo3 expression in human synovial fibroblasts by inhibiting mir-92a through ampk and p38 pathways","volume":"11","author":"Kuo","year":"2019","journal-title":"Aging"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s12938-019-0717-3","article-title":"Effects of computer-assisted navigation versus the conventional technique for total knee arthroplasty on levels of plasma thrombotic markers: A prospective study","volume":"18","author":"Siu","year":"2019","journal-title":"Biomed. Eng. Online"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.bbamcr.2012.12.023","article-title":"Ccn4 induces vascular cell adhesion molecule-1 expression in human synovial fibroblasts and promotes monocyte adhesion","volume":"1833","author":"Liu","year":"2013","journal-title":"Biochim. Et Biophys. Acta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1002\/art.24757","article-title":"Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints","volume":"60","author":"Schett","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_5","first-page":"544","article-title":"Association between vascular cell adhesion molecule 1 and radiographic hand osteoarthritis","volume":"29","author":"Kalichman","year":"2011","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1532164","DOI":"10.1155\/2019\/1532164","article-title":"An update on the emerging role of resistin on the pathogenesis of osteoarthritis","volume":"2019","author":"Zhao","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3109\/03009742.2013.853096","article-title":"Resistin as a factor in osteoarthritis: Synovial fluid resistin concentrations correlate positively with interleukin 6 and matrix metalloproteinases mmp-1 and mmp-3","volume":"43","author":"Koskinen","year":"2014","journal-title":"Scand. J. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, Y.H., Kuo, S.J., Liu, S.C., Wang, S.W., Tsai, C.H., Fong, Y.C., and Tang, C.H. (2020). Apelin affects the progression of osteoarthritis by regulating vegf-dependent angiogenesis and mir-150-5p expression in human synovial fibroblasts. Cells, 9.","DOI":"10.3390\/cells9030594"},{"key":"ref_9","first-page":"40","article-title":"The function of micrornas in cartilage and osteoarthritis","volume":"37","author":"Swingler","year":"2019","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1002\/art.39173","article-title":"Microrna-9 promotion of interleukin-6 expression by inhibiting monocyte chemoattractant protein-induced protein 1 expression in interleukin-1beta-stimulated human chondrocytes","volume":"67","author":"Makki","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kim, J.E., Song, D.H., Kim, S.H., Jung, Y., and Kim, S.J. (2018). Development and characterization of various osteoarthritis models for tissue engineering. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194288"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1002\/stem.2024","article-title":"Resistin promotes angiogenesis in endothelial progenitor cells through inhibition of microrna206: Potential implications for rheumatoid arthritis","volume":"33","author":"Su","year":"2015","journal-title":"Stem Cells"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1002\/tox.22618","article-title":"Glucose suppresses il-1beta-induced mmp-1 expression through the fak, mek, erk, and ap-1 signaling pathways","volume":"33","author":"Wu","year":"2018","journal-title":"Environ. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.bcp.2019.05.005","article-title":"Thrombospondin enhances rankl-dependent osteoclastogenesis and facilitates lung cancer bone metastasis","volume":"166","author":"Wang","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.bcp.2018.07.024","article-title":"Thrombospondin 2 promotes tumor metastasis by inducing matrix metalloproteinase-13 production in lung cancer cells","volume":"155","author":"Liu","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.jff.2018.11.040","article-title":"Plumbagin suppresses endothelial progenitor cell-related angiogenesis in vitro and in vivo","volume":"52","author":"Lee","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/09540105.2020.1713055","article-title":"Soya-cerebroside inhibits vegf-facilitated angiogenesis in endothelial progenitor cells","volume":"31","author":"Lee","year":"2020","journal-title":"Food Agric. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1080\/09540105.2019.1660623","article-title":"Glucocerebroside reduces endothelial progenitor cell-induced angiogenesis","volume":"30","author":"Lee","year":"2019","journal-title":"Food Agric. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.bcp.2018.05.001","article-title":"Resistin facilitates vegf-c-associated lymphangiogenesis by inhibiting mir-186 in human chondrosarcoma cells","volume":"154","author":"Su","year":"2018","journal-title":"Biochem. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12986-019-0356-5","article-title":"High-density lipoprotein ameliorates palmitic acid-induced lipotoxicity and oxidative dysfunction in h9c2 cardiomyoblast cells via ros suppression","volume":"16","author":"Wu","year":"2019","journal-title":"Nutr. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kuo, S.J., Yang, W.H., Liu, S.C., Tsai, C.H., Hsu, H.C., and Tang, C.H. (2017). Transforming growth factor beta1 enhances heme oxygenase 1 expression in human synovial fibroblasts by inhibiting microrna 519b synthesis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0176052"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/tox.22674","article-title":"Melatonin reduces lung cancer stemness through inhibiting of plc, erk, p38, beta-catenin, and twist pathways","volume":"34","author":"Yang","year":"2019","journal-title":"Environ. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"R210","DOI":"10.1186\/ar3543","article-title":"Application of in vivo micro-computed tomography in the temporal characterisation of subchondral bone architecture in a rat model of low-dose monosodium iodoacetate-induced osteoarthritis","volume":"13","author":"Mohan","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chien, S.Y., Tsai, C.H., Liu, S.C., Huang, C.C., Lin, T.H., Yang, Y.Z., and Tang, C.H. (2020). Noggin inhibits il-1beta and bmp-2 expression, and attenuates cartilage degeneration and subchondral bone destruction in experimental osteoarthritis. Cells, 9.","DOI":"10.3390\/cells9040927"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.4049\/jimmunol.1403191","article-title":"Osteopontin promotes oncostatin m production in human osteoblasts: Implication of rheumatoid arthritis therapy","volume":"195","author":"Su","year":"2015","journal-title":"J. Immunol"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1016\/j.joca.2010.05.030","article-title":"The oarsi histopathology initiative-recommendations for histological assessments of osteoarthritis in the rat","volume":"18","author":"Gerwin","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","article-title":"The oarsi histopathology initiative-recommendations for histological assessments of osteoarthritis in the mouse","volume":"18","author":"Glasson","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.joca.2020.01.007","article-title":"Macrophages regulate the progression of osteoarthritis","volume":"28","author":"Zhang","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.yjmcc.2007.08.009","article-title":"Resistin, an adipocytokine, offers protection against acute myocardial infarction","volume":"43","author":"Gao","year":"2007","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9767","DOI":"10.18632\/aging.102423","article-title":"Resistin enhances angiogenesis in osteosarcoma via the mapk signaling pathway","volume":"11","author":"Tsai","year":"2019","journal-title":"Aging"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11914-018-0417-0","article-title":"Regulation of bone metabolism by micrornas","volume":"16","author":"Taipaleenmaki","year":"2018","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_32","first-page":"162","article-title":"Melatonin rescued interleukin 1beta-impaired chondrogenesis of human mesenchymal stem cells","volume":"9","author":"Gao","year":"2018","journal-title":"Stem Cell Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1080\/09540105.2019.1611745","article-title":"Soya-cerebroside reduces il-1 beta-induced mmp-1 production in chondrocytes and inhibits cartilage degradation: Implications for the treatment of osteoarthritis","volume":"30","author":"Liu","year":"2019","journal-title":"Food Agric. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1517\/14712598.5.3.313","article-title":"Involvement of icam-1 in bone metabolism: A potential target in the treatment of bone diseases?","volume":"5","author":"Lavigne","year":"2005","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/jcla.21876","article-title":"Possible involvement of serum and synovial fluid resistin in knee osteoarthritis: Cartilage damage, clinical, and radiological links","volume":"30","author":"Song","year":"2016","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3389\/fphar.2018.00071","article-title":"Convenience versus biological significance: Are pma-differentiated thp-1 cells a reliable substitute for blood-derived macrophages when studying in vitro polarization?","volume":"9","author":"Tedesco","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.joca.2012.08.027","article-title":"Synovial inflammation, immune cells and their cytokines in osteoarthritis: A review","volume":"20","author":"Zuurmond","year":"2012","journal-title":"Osteoarthr. Cartil."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/art.27290","article-title":"The role of synovial macrophages and macrophage-produced mediators in driving inflammatory and destructive responses in osteoarthritis","volume":"62","author":"Bondeson","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3389\/fimmu.2011.00052","article-title":"Macrophages in synovial inflammation","volume":"2","author":"Kennedy","year":"2011","journal-title":"Front. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.atherosclerosis.2017.02.021","article-title":"Pkc-epsilon and tlr4 synergistically regulate resistin-mediated inflammation in human macrophages","volume":"259","author":"Zuniga","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chen, H.T., Tsou, H.K., Chen, J.C., Shih, J.M., Chen, Y.J., and Tang, C.H. (2014). Adiponectin enhances intercellular adhesion molecule-1 expression and promotes monocyte adhesion in human synovial fibroblasts. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0092741"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1478-811X-11-68","article-title":"Amp-activated protein kinase activation mediates ccl3-induced cell migration and matrix metalloproteinase-2 expression in human chondrosarcoma","volume":"11","author":"Hsu","year":"2013","journal-title":"Cell Commun. Signal. CCS"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.joca.2015.10.018","article-title":"Micrornas: Exploring new horizons in osteoarthritis","volume":"24","author":"Nugent","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.omtn.2019.07.011","article-title":"Multi-pathway protective effects of micrornas on human chondrocytes in an in vitro model of osteoarthritis","volume":"17","author":"Brinchmann","year":"2019","journal-title":"Mol. Nucleic Acids"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/6\/1369\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:34:39Z","timestamp":1760175279000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/6\/1369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,1]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["cells9061369"],"URL":"https:\/\/doi.org\/10.3390\/cells9061369","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,1]]}}}