{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:50:05Z","timestamp":1762080605182,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Qinghai Tibet Plateau Research Institute, Chinese Academy of Sciences","award":["2019QZKK0607"],"award-info":[{"award-number":["2019QZKK0607"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>C-X-C motif chemokine receptor 4 (CXCR4), stromal cell-derived factor-1 (SDF-1), monocyte chemoattractant protein-1 (MCP-1), extracellular signal-regulated kinase 1\/2 (ERK1\/2) and nuclear factor-\u03baB (NF-\u03baB) affect bone cells and play an important role in bone and joint diseases, but the data on CXCR4, SDF-1, MCP-1, ERK1\/2 and NF-\u03baB in the serum of skeletal fluorosis (SF) patients are inconclusive. Thus, according to the \u201cDiagnostic Criteria for Endemic Skeletal Fluorosis\u201d (WS 192-2008), we enrolled patients with SF (n = 60) as the SF group and those without SF as the controls (n = 60). Serum levels of CXCR4, SDF-1, MCP-1, ERK1\/2 and NF-\u03baB were detected by enzyme-linked immunosorbent assays (ELISAs). Serum SDF-1, CXCR4, MCP-1 and NF-\u03baB levels were significantly higher in the SF group than in the control group. Within the serum of SF patients, CXCR4 and SDF-1 levels were positively correlated with NF-\u03baB levels. There was no correlation between MCP-1 levels and those of ERK1\/2 or NF-\u03baB. SDF-1 and CXCR4 may activate the NF-\u03baB pathway, and MCP-1 affects the occurrence and development of SF by regulating osteocytes through other pathways. The SDF-1\/CXCR4 axis and MCP-1 signalling pathway provide a new theoretical basis for the occurrence and development of SF.<\/jats:p>","DOI":"10.3390\/ijerph192416555","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T06:14:00Z","timestamp":1670566440000},"page":"16555","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Serum Levels of CXCR4, SDF-1, MCP-1, NF-\u03baB and ERK1\/2 in Patients with Skeletal Fluorosis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0474-5419","authenticated-orcid":false,"given":"Yaqian","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Public Health, Medical College, Qinghai University, Xi\u2019ning 810016, China"},{"name":"Department of Endemic Disease Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control, Xi\u2019ning 811602, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanglan","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Endemic Disease Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control, Xi\u2019ning 811602, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endemic Disease Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control, Xi\u2019ning 811602, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Endemic Disease Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control, Xi\u2019ning 811602, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Public Health, Medical College, Qinghai University, Xi\u2019ning 810016, China"},{"name":"Department of Endemic Disease Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control, Xi\u2019ning 811602, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endemic Disease Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control, Xi\u2019ning 811602, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Endemic Disease Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control, Xi\u2019ning 811602, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endemic Disease Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control, Xi\u2019ning 811602, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Public Health, Medical College, Qinghai University, Xi\u2019ning 810016, China"},{"name":"Department of Endemic Disease Prevention and Control, Qinghai Institute for Endemic Disease Prevention and Control, Xi\u2019ning 811602, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1007\/s00204-020-02687-5","article-title":"Principles of fluoride toxicity and the cellular response: A review","volume":"94","author":"Johnston","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.cbi.2010.07.011","article-title":"Molecular mechanisms of fluoride toxicity","volume":"188","author":"Barbier","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_3","first-page":"142","article-title":"The State and Trend of Endemic Fluorosis from 1991 to 2012 in China","volume":"33","author":"Liu","year":"2016","journal-title":"J. Chongqing Norm. Univ. (Nat. Sci. Ed.)"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/tox.21784","article-title":"Fluoride decreased osteoclastic bone resorption through the inhibition of NFATc1 gene expression","volume":"29","author":"Pei","year":"2014","journal-title":"Environ. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.tox.2017.11.009","article-title":"The role of TGFbeta receptor 1-smad3 signaling in regulating the osteoclastic mode affected by fluoride","volume":"393","author":"Yu","year":"2018","journal-title":"Toxicology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/0277-9536(94)00429-W","article-title":"Outline of control practice of endemic fluorosis in China","volume":"41","author":"Wang","year":"1995","journal-title":"Soc. Sci. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s00586-006-0242-5","article-title":"Thoracic ossification of ligamentum flavum caused by skeletal fluorosis","volume":"16","author":"Wang","year":"2007","journal-title":"Eur. Spine J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1111\/jcmm.14185","article-title":"The pathogenesis of endemic fluorosis: Research progress in the last 5 years","volume":"23","author":"Wei","year":"2019","journal-title":"J. Cell Mol. Med."},{"key":"ref_9","first-page":"158","article-title":"The role of SDF-1\/CXCR4 and downstream signaling pathways in the course","volume":"9","author":"Mou","year":"2011","journal-title":"J. Pract. Med."},{"key":"ref_10","first-page":"491","article-title":"Expression of Fas, FasL, and NF-\u03baB in the Process of Osteoclast-like Cell Apoptosis Effected by Sodium Fluoride","volume":"24","author":"Sun","year":"2002","journal-title":"J. Chin. Acad. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2008.03.002","article-title":"Effects of fluoride on DNA damage, S-phase cell-cycle arrest and the expression of NF-kappaB in primary cultured rat hippocampal neurons","volume":"179","author":"Zhang","year":"2008","journal-title":"Toxicol. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.matbio.2007.06.002","article-title":"JNK\/c-Jun signaling pathway mediates the fluoride-induced down-regulation of MMP-20 in vitro","volume":"26","author":"Zhang","year":"2007","journal-title":"Matrix Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/0022034509334771","article-title":"NaF activates MAPKs and induces apoptosis in odontoblast-like cells","volume":"88","author":"Karube","year":"2009","journal-title":"J. Dent. Res."},{"key":"ref_14","first-page":"3563","article-title":"The role of SDF-1\/CXCR4 and downstream signaling pathways in the course of OA","volume":"35","author":"He","year":"2019","journal-title":"J. Pract. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3389\/fendo.2017.00022","article-title":"Environmental Factors Impacting Bone-Relevant Chemokines","volume":"8","author":"Smith","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/164_2020_349","article-title":"Chemokines and Bone","volume":"262","author":"Gilchrist","year":"2020","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_17","first-page":"204","article-title":"The role of C-C motif chemokine ligand 2 in respiratory diseases","volume":"45","author":"Yang","year":"2018","journal-title":"Int. J. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3389\/fimmu.2015.00301","article-title":"CXCL12\/SDF-1 and CXCR4","volume":"6","author":"Nagasawa","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1023\/B:HIJO.0000032355.66152.b8","article-title":"CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion","volume":"35","author":"Kucia","year":"2004","journal-title":"J. Mol. Histol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S1359-6101(01)00014-4","article-title":"Chemokine receptors","volume":"12","author":"Horuk","year":"2001","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1177\/1753425919895086","article-title":"Serum CXCL12\/SDF-1 level is positively related with lumbar intervertebral disc degeneration and clinical severity","volume":"26","author":"Er","year":"2020","journal-title":"Innate Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"154783","DOI":"10.1016\/j.cyto.2019.154783","article-title":"Stromal cell-derived factor-1 (CXCL12) and its role in bone and muscle biology","volume":"123","author":"Gilbert","year":"2019","journal-title":"Cytokine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.joca.2020.10.010","article-title":"The role of stromal cell-derived factor 1 on cartilage development and disease","volume":"29","author":"Li","year":"2021","journal-title":"Osteoarthr. Cartil."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1359\/jbmr.2003.18.8.1404","article-title":"Stromal cell-derived factor-1 (SDF-1) recruits osteoclast precursors by inducing chemotaxis, matrix metalloproteinase-9 (MMP-9) activity, and collagen transmigration","volume":"18","author":"Yu","year":"2003","journal-title":"J. Bone Min. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.3389\/fimmu.2019.02759","article-title":"More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis","volume":"10","author":"Gschwandtner","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.3389\/fimmu.2019.02182","article-title":"Chemokines in Physiological and Pathological Bone Remodeling","volume":"10","author":"Brylka","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_27","first-page":"964","article-title":"Research Developments of Monocyte Chemoattractant Protein-1 in Inflammatory Reaction","volume":"19","author":"Mao","year":"2013","journal-title":"Med. Recapitul."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nm.1945","article-title":"Estrogen-dependent and C-C chemokine receptor-2-dependent pathways determine osteoclast behavior in osteoporosis","volume":"15","author":"Binder","year":"2009","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1002\/jcp.22879","article-title":"Absence of MCP-1 leads to elevated bone mass via impaired actin ring formation","volume":"227","author":"Sul","year":"2012","journal-title":"J. Cell Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fendo.2017.00049","article-title":"CCL2\/Monocyte Chemoattractant Protein 1 and Parathyroid Hormone Action on Bone","volume":"8","author":"Siddiqui","year":"2017","journal-title":"Front. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.bbamcr.2006.10.005","article-title":"The MEK\/ERK cascade: From signaling specificity to diverse functions","volume":"1773","author":"Shaul","year":"2007","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lu, N., and Malemud, C.J. (2019). Extracellular Signal-Regulated Kinase: A Regulator of Cell Growth, Inflammation, Chondrocyte and Bone Cell Receptor-Mediated Gene Expression. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153792"},{"key":"ref_33","first-page":"35","article-title":"Thyrocalcitonin regulates the cbfa1mRNA expression of osteoblasts via signal pathway of ERK-MAPK","volume":"13","author":"Zheng","year":"2009","journal-title":"J. Clin. Med. Pract."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.joca.2015.01.016","article-title":"CXC chemokine ligand 12a enhances chondrocyte proliferation and maturation during endochondral bone formation","volume":"23","author":"Kim","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_35","first-page":"1638","article-title":"Expression of stromal cell-derived factor 1, CXCR4 and ERK1\/2 in pathologic scar tissue","volume":"18","author":"Ma","year":"2009","journal-title":"Chin. J. Aesthetic Med."},{"key":"ref_36","first-page":"30","article-title":"Function of NF-\u03baB Signaling Pathway in Bone and Bone Diseases","volume":"23","author":"Cao","year":"2015","journal-title":"Sichuan J. Anat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/cr.2010.159","article-title":"Role of NF-kappaB in the skeleton","volume":"21","author":"Novack","year":"2011","journal-title":"Cell Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S8756-3282(99)00105-2","article-title":"Required and nonessential functions of nuclear factor-kappa B in bone cells","volume":"25","author":"Boyce","year":"1999","journal-title":"Bone"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1007\/s00198-013-2313-x","article-title":"NF-kappaB signaling and bone resorption","volume":"24","year":"2013","journal-title":"Osteoporos. Int."},{"key":"ref_40","unstructured":"Chen, P. (2012). To Investigate the Tea-Based Fluorosis in Qinghai Province. [Master\u2019s Thesis, Shanxi Medical University]."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.bone.2004.03.019","article-title":"Inhibition of growth and differentiation of osteoprogenitors in mouse bone marrow stromal cell cultures by increased donor age and glucocorticoid treatment","volume":"35","author":"Chen","year":"2004","journal-title":"Bone"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1177\/1753425919883365","article-title":"Elevated plasma CXCL12\/SDF-1 levels are linked with disease severity of postmenopausal osteoporosis","volume":"26","author":"Yang","year":"2020","journal-title":"Innate Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"240","DOI":"10.7150\/ijms.7489","article-title":"Stromal cell-derived factor-1 and its receptor CXCR4 are upregulated expression in degenerated intervertebral discs","volume":"11","author":"Zhang","year":"2014","journal-title":"Int. J. Med. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bragg, R., Gilbert, W., Elmansi, A.M., Isales, C.M., Hamrick, M.W., Hill, W.D., and Fulzele, S. (2019). Stromal cell-derived factor-1 as a potential therapeutic target for osteoarthritis and rheumatoid arthritis. Ther. Adv. Chronic. Dis., 10.","DOI":"10.1177\/2040622319882531"},{"key":"ref_45","first-page":"1925","article-title":"Expression Levels of CXCR4 and CXCL12 in Patients with Rheumatoid Arthritis and its Correlation with Disease Activity","volume":"20","author":"Peng","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4508108","DOI":"10.1155\/2020\/4508108","article-title":"miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway","volume":"2020","author":"Xiang","year":"2020","journal-title":"Biochem. Res. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1136\/annrheumdis-2016-210426","article-title":"CCL2\/CCR2, but not CCL5\/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis","volume":"76","author":"Raghu","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_48","unstructured":"Gao, J. (2020). Effect of CASR\/MAPK Signaling Pathway on the Pathogenesis of Fluorosis. [Master\u2019s Thesis, Jilin University]."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5807","DOI":"10.3892\/mmr.2017.7366","article-title":"Electroacupuncture serum inhibits TNF-\u03b1-mediated chondrocyte inflammation via the Ras-Raf-MEK1\/2-ERK1\/2 signaling pathway","volume":"16","author":"Chen","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1111\/os.12745","article-title":"Chondroprotective Effect of Wufu Decoction on Tumor Necrosis Factor-alpha-Induced Chondrocytes via the Extracellular Signal Regulated Kinase 1\/2 Signaling Pathway","volume":"12","author":"Ye","year":"2020","journal-title":"Orthop. Surg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1559325818800153","DOI":"10.1177\/1559325818800153","article-title":"Amelioration of the Protein Expression of Cox2, NFkappaB, and STAT-3 by Some Antioxidants in the Liver of Sodium Fluoride-Intoxicated Rats","volume":"16","author":"Alhusaini","year":"2018","journal-title":"Dose Response"},{"key":"ref_52","first-page":"98","article-title":"Research Progress on the Role of CCL2 and Its Signal Pathway in the Pathogenesis of Rheumatoid Arthritis and Periodontitis","volume":"60","author":"Zhang","year":"2020","journal-title":"Shandong Med. J."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/24\/16555\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:37:13Z","timestamp":1760146633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/24\/16555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,9]]},"references-count":52,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijerph192416555"],"URL":"https:\/\/doi.org\/10.3390\/ijerph192416555","relation":{},"ISSN":["1660-4601"],"issn-type":[{"type":"electronic","value":"1660-4601"}],"subject":[],"published":{"date-parts":[[2022,12,9]]}}}