{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T13:55:34Z","timestamp":1764251734721,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T00:00:00Z","timestamp":1642204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology of Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2314-B-182A-105 -MY3"],"award-info":[{"award-number":["MOST 108-2314-B-182A-105 -MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chang-Gung Memorial Foundation","award":["CMRPG8J0411"],"award-info":[{"award-number":["CMRPG8J0411"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Psoriatic arthritis (PsA) results from joint destruction by osteoclasts. The promising efficacy of TNF-\u03b1 blockage indicates its important role in osteoclastogenesis of PsA. WNT ligands actively regulate osteoclastogenesis. We investigated how WNT ligands activate osteoclasts amid the TNF-\u03b1 milieu in PsA. We first profiled the expression of WNT ligands in CD14+ monocyte-derived osteoclasts (MDOC) from five PsA patients and five healthy controls (HC) and then validated the candidate WNT ligands in 32 PsA patients and 16 HC. Through RNA interference against WNT ligands in MDOC, we determined the mechanisms by which TNF-\u03b1 exerts its effects on osteclastogenesis or chemotaxis. WNT5A was selectively upregulated by TNF-\u03b1 in MDOC from PsA patients. The number of CD68+WNT5A+ osteoclasts increased in PsA joints. CXCL1, CXCL16, and MCP-1 was selectively increased in supernatants of MDOC from PsA patients. RNA interference against WNT5A abolished the increased MCP-1 from MDOC and THP-1-cell-derived osteoclasts. The increased migration of osteoclast precursors (OCP) induced by supernatant from PsA MDOC was abolished by the MCP-1 neutralizing antibody. WNT5A and MCP-1 expressions were decreased in MDOC from PsA patients treated by biologics against TNF-\u03b1 but not IL-17. We conclude that TNF-\u03b1 recruits OCP by increased MCP-1 production but does not directly activate osteoclastogenesis in PsA.<\/jats:p>","DOI":"10.3390\/ijms23020921","type":"journal-article","created":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T20:44:00Z","timestamp":1642365840000},"page":"921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["TNF-\u03b1 Activating Osteoclasts in Patients with Psoriatic Arthritis Enhances the Recruitment of Osteoclast Precursors: A Plausible Role of WNT5A-MCP-1 in Osteoclast Engagement in Psoriatic Arthritis"],"prefix":"10.3390","volume":"23","author":[{"given":"Shang-Hung","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Chen","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Chiayi Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Chiayi 613, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3016-9718","authenticated-orcid":false,"given":"Sung-Chou","family":"Li","sequence":"additional","affiliation":[{"name":"Genomics and Proteomics Core Laboratory, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Wen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1207-646X","authenticated-orcid":false,"given":"Chung-Yuan","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Yi","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7275-4675","authenticated-orcid":false,"given":"Chang-Chun","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9804-3874","authenticated-orcid":false,"given":"Chih-Hung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1056\/NEJMra1505557","article-title":"Psoriatic Arthritis","volume":"376","author":"Ritchlin","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1016\/S0140-6736(18)30830-4","article-title":"The pathogenesis of psoriatic arthritis","volume":"391","author":"Veale","year":"2018","journal-title":"Lancet"},{"key":"ref_3","first-page":"634","article-title":"The diagnosis and treatment of early psoriatic arthritis. Nature reviews","volume":"5","author":"Anandarajah","year":"2009","journal-title":"Rheumatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1126\/science.289.5484.1504","article-title":"Bone resorption by osteoclasts","volume":"289","author":"Teitelbaum","year":"2000","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1046\/j.1365-2141.1999.01491.x","article-title":"Human osteoclasts derive from CD14-positive monocytes","volume":"106","author":"Massey","year":"1999","journal-title":"Br. J. Haematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s10875-009-9316-6","article-title":"Osteoimmunology: Crosstalk between the immune and bone systems","volume":"29","author":"Nakashima","year":"2009","journal-title":"J. Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/jbmr.531","article-title":"Regulation of human osteoclast development by dendritic cell-specific transmembrane protein (DC-STAMP)","volume":"27","author":"Chiu","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1172\/JCI200316069","article-title":"Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis","volume":"111","author":"Ritchlin","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1074-7613(03)00174-2","article-title":"Blood monocytes consist of two principal subsets with distinct migratory properties","volume":"19","author":"Geissmann","year":"2003","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R152","DOI":"10.1186\/ar2046","article-title":"Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts","volume":"8","author":"Komano","year":"2006","journal-title":"Arthritis Res. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Matsubara, R., Kukita, T., Ichigi, Y., Takigawa, I., Qu, P.F., Funakubo, N., Miyamoto, H., Nonaka, K., and Kukita, A. (2012). Characterization and identification of subpopulations of mononuclear preosteoclasts induced by TNF-alpha in combination with TGF-beta in rats. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047930"},{"key":"ref_12","first-page":"2432","article-title":"Localized monocyte chemotactic protein-1 production correlates with T cell infiltration of synovium in patients with psoriatic arthritis","volume":"27","author":"Ross","year":"2000","journal-title":"J. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1136\/ard.2004.020529","article-title":"Chemokines in joint disease: The key to inflammation?","volume":"63","author":"Haringman","year":"2004","journal-title":"Ann. Rheum. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1111\/joim.12368","article-title":"The WNT system: Background and its role in bone","volume":"277","author":"Lerner","year":"2015","journal-title":"J. Intern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nm.2653","article-title":"Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis","volume":"18","author":"Maeda","year":"2012","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20764","DOI":"10.1073\/pnas.0805133106","article-title":"Regulation of bone formation by osteoclasts involves Wnt\/BMP signaling and the chemokine sphingosine-1-phosphate","volume":"105","author":"Pederson","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1128\/MCB.05980-11","article-title":"Biphasic and dosage-dependent regulation of osteoclastogenesis by beta-catenin","volume":"31","author":"Wei","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.bbrc.2011.11.089","article-title":"Noncanonical Wnt signaling promotes osteoclast differentiation and is facilitated by the human immunodeficiency virus protease inhibitor ritonavir","volume":"417","author":"Santiago","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1073\/pnas.050574297","article-title":"Expression and function of wingless and frizzled homologs in rheumatoid arthritis","volume":"97","author":"Sen","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5876","DOI":"10.1111\/jcmm.14531","article-title":"The pathological role of Wnt5a in psoriasis and psoriatic arthritis","volume":"23","author":"Tian","year":"2019","journal-title":"J. Cell Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jdermsci.2018.05.009","article-title":"Treatment with TNF-alpha inhibitor rectifies M1 macrophage polarization from blood CD14+ monocytes in patients with psoriasis independent of STAT1 and IRF-1 activation","volume":"91","author":"Lin","year":"2018","journal-title":"J. Dermatol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1002\/art.40468","article-title":"Inflammation Intensity-Dependent Expression of Osteoinductive Wnt Proteins Is Critical for Ectopic New Bone Formation in Ankylosing Spondylitis","volume":"70","author":"Li","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21028","DOI":"10.1074\/jbc.M113.546523","article-title":"Wnt5a promotes inflammatory responses via nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) pathways in human dental pulp cells","volume":"289","author":"Zhao","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.trsl.2015.06.010","article-title":"Wnt5a is expressed in spondyloarthritis and exerts opposite effects on enthesis and bone in murine organ and cell cultures","volume":"166","author":"Bougault","year":"2015","journal-title":"Transl. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"eaan0023","DOI":"10.1126\/scisignal.aan0023","article-title":"Protein kinase N3 promotes bone resorption by osteoclasts in response to Wnt5a-Ror2 signaling","volume":"10","author":"Uehara","year":"2017","journal-title":"Sci. Signal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3683","DOI":"10.1007\/s00018-018-2881-1","article-title":"Non-canonical Wnt signals regulate cytoskeletal remodeling in osteoclasts","volume":"75","author":"Uehara","year":"2018","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhao, C., Bu, X., Wang, W., Ma, T., and Ma, H. (2014). GEC-derived SFRP5 inhibits Wnt5a-induced macrophage chemotaxis and activation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085058"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s004280050472","article-title":"Mig, GRO alpha and RANTES messenger RNA expression in lining layer, infiltrates and different leucocyte populations of synovial tissue from patients with rheumatoid arthritis, psoriatic arthritis and osteoarthritis","volume":"436","author":"Konig","year":"2000","journal-title":"Virchows Arch."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1136\/annrheumdis-2018-214737","article-title":"Serum-based soluble markers differentiate psoriatic arthritis from osteoarthritis","volume":"78","author":"Chandran","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/art.41156","article-title":"Polyfunctional, Proinflammatory, Tissue-Resident Memory Phenotype and Function of Synovial Interleukin-17A+CD8+ T Cells in Psoriatic Arthritis","volume":"72","author":"Steel","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s10585-015-9714-5","article-title":"Marrow adipocyte-derived CXCL1 and CXCL2 contribute to osteolysis in metastatic prostate cancer","volume":"32","author":"Hardaway","year":"2015","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.bone.2007.11.016","article-title":"Activation of peroxisome proliferator-activated receptor gamma inhibits TNF-alpha-mediated osteoclast differentiation in human peripheral monocytes in part via suppression of monocyte chemoattractant protein-1 expression","volume":"42","author":"Hounoki","year":"2008","journal-title":"Bone"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1210\/endo.136.6.7750500","article-title":"Monocyte chemoattractant protein-1 expression and monocyte recruitment in osseous inflammation in the mouse","volume":"136","author":"Rahimi","year":"1995","journal-title":"Endocrinology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1089\/jir.2008.0027","article-title":"Monocyte chemoattractant protein-1 (MCP-1): An overview","volume":"29","author":"Deshmane","year":"2009","journal-title":"J. Interferon. Cytokine Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1038\/s41467-018-06933-4","article-title":"Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis","volume":"9","author":"Cambre","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2334\/josnusd.17-0187","article-title":"The effect of mesenchymal stem cells on chemotaxis of osteoclast precursor cells","volume":"60","author":"Sumi","year":"2018","journal-title":"J. Oral. Sci"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nm.3260","article-title":"How cytokine networks fuel inflammation: Toward a cytokine-based disease taxonomy","volume":"19","author":"Schett","year":"2013","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1136\/ard.2007.076091","article-title":"The effect of etanercept on osteoclast precursor frequency and enhancing bone marrow oedema in patients with psoriatic arthritis","volume":"67","author":"Anandarajah","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/acr2.11094","article-title":"Responses to Cytokine Inhibitors Associated with Cellular Composition in Models of Immune-Mediated Inflammatory Arthritis","volume":"2","author":"Nielsen","year":"2020","journal-title":"ACR Open Rheumatol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/921\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:15:04Z","timestamp":1760364904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,15]]},"references-count":39,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23020921"],"URL":"https:\/\/doi.org\/10.3390\/ijms23020921","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,1,15]]}}}