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CCL2 is a member of the CC chemokine superfamily, which binds to its receptor, C\u2010C motif chemokine receptor\u20102 (CCR2), for the induction of chemotactic activity\u00a0and an increase of calcium influx. It exerts multiple effects on a variety of cells, including monocytes, macrophages, osteoclasts, basophils, and endothelial cells, and is involved in a diverse range of diseases. This review discusses the molecular structure and role of CCL2 and CCR2 in skeletal biology and disease. Molecular structure analyses reveal that CCL2 shares a conserved C\u2010C motif; however, it has only limited sequence homology with other CCL family members. Likewise, CCR2, as a member of the G\u2010protein\u2010coupled seven\u2010transmembrane receptor superfamily, shares conserved cysteine residues, but exhibits very limited sequence homology with other CCR family members. In the skeletal system, the expression of CCL2 is regulated by a variety of factors, such as parathyroid hormone\/parathyroid hormone\u2010related peptide, interleukin 1b, tumor necrosis factor\u2010\u03b1 and transforming growth factor\u2010beta, RANKL, and mechanical forces. The interaction of CCL2 and CCR2 activates several signaling cascades, including PI3K\/Akt\/ERK\/NF\u2010\u03baB, PI3K\/MAPKs, and JAK\/STAT\u20101\/STAT\u20103. Understanding the role of CCL2 and CCR2 will facilitate the development of novel therapies for skeletal disorders, including rheumatoid arthritis, osteolysis and other inflammatory diseases related to abnormal chemotaxis.<\/jats:p>","DOI":"10.1002\/jcp.30375","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T05:05:59Z","timestamp":1617080759000},"page":"7211-7222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["The molecular structure and role of CCL2 (MCP\u20101) and C\u2010C chemokine receptor CCR2 in skeletal biology and diseases"],"prefix":"10.1002","volume":"236","author":[{"given":"Sipin","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"School of Biomedical Sciences The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4960-0096","authenticated-orcid":false,"given":"Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The University of Western Australia  Perth Western Australia Australia"},{"name":"Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences Nanjing Normal University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Bennett","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8261-9189","authenticated-orcid":false,"given":"Kevin D. 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