Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia.
J Cell Physiol. 2021 Oct;236(10):7211-7222. doi: 10.1002/jcp.30375. Epub 2021 Mar 30.
Monocyte chemoattractant protein-1, also called chemokine (C-C motif) ligand 2 (CCL2) or small inducible cytokine A2, is an inflammatory mediator capable of recruiting monocytes, memory T cells, and dendritic cells. CCL2 is a member of the CC chemokine superfamily, which binds to its receptor, C-C motif chemokine receptor-2 (CCR2), for the induction of chemotactic activity and 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-C motif; however, it has only limited sequence homology with other CCL family members. Likewise, CCR2, as a member of the G-protein-coupled seven-transmembrane 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-related peptide, interleukin 1b, tumor necrosis factor-α and transforming growth factor-beta, RANKL, and mechanical forces. The interaction of CCL2 and CCR2 activates several signaling cascades, including PI3K/Akt/ERK/NF-κB, PI3K/MAPKs, and JAK/STAT-1/STAT-3. 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.
单核细胞趋化蛋白-1，也称为趋化因子（C-C 基元）配体 2（CCL2）或小诱导细胞因子 A2，是一种能够募集单核细胞、记忆 T 细胞和树突状细胞的炎症介质。CCL2 是 CC 趋化因子超家族的成员，它与受体 C-C 基元趋化因子受体 2（CCR2）结合，诱导趋化活性和钙内流增加。它对多种细胞（包括单核细胞、巨噬细胞、破骨细胞、嗜碱性粒细胞和内皮细胞）产生多种影响，并参与多种疾病。本综述讨论了 CCL2 和 CCR2 在骨骼生物学和疾病中的分子结构和作用。分子结构分析表明，CCL2 具有保守的 C-C 基元；然而，它与其他 CCL 家族成员只有有限的序列同源性。同样，CCR2 作为 G 蛋白偶联七跨膜受体超家族的成员，共享保守的半胱氨酸残基，但与其他 CCR 家族成员的序列同源性非常有限。在骨骼系统中，CCL2 的表达受多种因素的调节，如甲状旁腺激素/甲状旁腺激素相关肽、白细胞介素 1b、肿瘤坏死因子-α和转化生长因子-β、RANKL 和机械力。CCL2 和 CCR2 的相互作用激活了几种信号通路，包括 PI3K/Akt/ERK/NF-κB、PI3K/MAPKs 和 JAK/STAT-1/STAT-3。了解 CCL2 和 CCR2 的作用将有助于开发治疗骨骼疾病的新疗法，包括类风湿关节炎、骨溶解和其他与异常趋化有关的炎症性疾病。
