CCL4 enhances preosteoclast migration and its receptor CCR5 downregulation by RANKL promotes osteoclastogenesis

Chemokine CCL4 (MIP-1β) is released from osteoblast cells to restore the homeostasis of hematopoietic stem cells during the activation of bone marrow. In this study, we investigated the function of CCL4 and its receptor CCR5 during osteoclastogenesis. CCL4 promoted the migration and viability of preosteoclast cells. However, CCL4 had no direct effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in mouse preosteoclast cells. In addition, CCR5 expression was rapidly reduced by RANKL treatment, which was recovered by IFN-γ during osteoclastogenesis. CCR5 downregulation by RANKL was mediated by MEK and JNK in preosteoclast cells and promoted osteoclastogenesis. These results suggest that CCL4 can enhance the recruitment of preosteoclasts to bone in the early stage, and the reduction of CCR5 promotes osteoclastogenesis when RANKL is prevalent.

• Publication year

  2018

• Venue

  Cell Death and Disease

• Publication date

  2018-05-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/s41419-018-0562-5PMID 29717113PMCID 5931580
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Cell Viability Assays

  2016cited by this paper
• Downregulation of CCR5 inhibits the proliferation and invasion of cervical cancer cells and is regulated by microRNA-107.

  2016cited by this paper
• Modulating the stem cell niche for tissue regeneration

  2014cited by this paper
• Hematopoietic stem cell niche maintenance during homeostasis and regeneration

  2014cited by this paper
• The CCL5/CCR5 axis promotes metastasis in basal breast cancer

  2013cited by this paper
• C-C chemokine receptor type five (CCR5): An emerging target for the control of HIV infection☆

  2013cited by this paper
• Regulation of postnatal bone homeostasis by TGFβ.

  2013cited by this paper
• CCL3 and CCL4 secretion by T regulatory cells attracts CD4+ and CD8+ T cells (P1077)

  2013cited by this paper
• Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration

  2013cited by this paper
• Genetic and Epigenetic Regulation of CCR5 Transcription

  2012cited by this paper
• RANKL downregulates cell surface CXCR6 expression through JAK2/STAT3 signaling pathway during osteoclastogenesis.

  2012cited by this paper
• Activated expression of the chemokine Mig after chemotherapy contributes to chemotherapy-induced bone marrow suppression and lethal toxicity.

  2012cited by this paper
• Inflammatory signals regulate hematopoietic stem cells.

  2011cited by this paper
• Irradiation induces bone injury by damaging bone marrow microenvironment for stem cells

  2011cited by this paper
• Polymerization of MIP‐1 chemokine (CCL3 and CCL4) and clearance of MIP‐1 by insulin‐degrading enzyme

  2010cited by this paper
• Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair.

  2009cited by this paper
• Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption1

  2009cited by this paper
• Faculty Opinions recommendation of Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair.

  2009cited by this paper
• IFNα activates dormant haematopoietic stem cells in vivo

  2009cited by this paper
• Bone Marrow-Derived Macrophages (BMM): Isolation and Applications.

  2008cited by this paper
• The Role of NFAT in Osteoclast Formation

  2007cited by this paper
• Osteoclast differentiation and gene regulation.

  2007cited by this paper
• CCL20 chemokine induces both osteoblast proliferation and osteoclast differentiation: Increased levels of CCL20 are expressed in subchondral bone tissue of rheumatoid arthritis patients

  2007cited by this paper
• Homeostatic chemokines increase survival of B-chronic lymphocytic leukemia cells through inactivation of transcription factor FOXO3a

  2007cited by this paper
• Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche.

  2007cited by this paper
• RANKL-induced down-regulation of CX3CR1 via PI3K/Akt signaling pathway suppresses Fractalkine/CX3CL1-induced cellular responses in RAW264.7 cells.

  2007cited by this paper
• RANKL-RANK signaling in osteoclastogenesis and bone disease.

  2006cited by this paper
• Chemokine and chemokine receptor expression during colony stimulating factor-1-induced osteoclast differentiation in the toothless osteopetrotic rat: a key role for CCL9 (MIP-1gamma) in osteoclastogenesis in vivo and in vitro.

  2006cited by this paper
• Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches.

  2006cited by this paper
• Chemokine and chemokine receptor expression during colony stimulating factor-1-induced osteoclast differentiation in the toothless osteopetrotic rat: a key role for CCL9 (MIP-1γ) in osteoclastogenesis in vivo and in vitro. Running head: CCL9 in osteoclastogenesis

  2005cited by this paper
• Variants of CCR5, which are permissive for HIV-1 infection, show distinct functional responses to CCL3, CCL4 and CCL5

  2005cited by this paper
• Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1

  2005cited by this paper
• Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis

  2004cited by this paper
• Osteoclast differentiation and activation

  2003cited by this paper
• Upregulation of expression of the chemokine receptor CCR5 by hydrogen peroxide in human monocytes.

  2003cited by this paper
• Macrophage inflammatory protein-1.

  2002cited by this paper
• Natural Truncation of the Chemokine MIP-1β/CCL4 Affects Receptor Specificity but Not Anti-HIV-1 Activity*

  2002cited by this paper
• CCL9/MIP‐1γ and its receptor CCR1 are the major chemokine ligand/receptor species expressed by osteoclasts

  2002cited by this paper
• B cells and professional APCs recruit regulatory T cells via CCL4

  2001cited by this paper
• The molecular basis of osteoclast differentiation and activation.

  2001cited by this paper
• Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

  2001cited by this paper
• Up-regulation of HIV coreceptors CXCR4 and CCR5 on CD4(+) T cells during human endotoxemia and after stimulation with (myco)bacterial antigens: the role of cytokines.

  2000cited by this paper
• T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ

  2000cited by this paper
• T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma.

  2000cited by this paper
• Interferon-γ Upregulates CCR5 Expression in Cord and Adult Blood Mononuclear Phagocytes

  1999cited by this paper
• Interferon-gamma upregulates CCR5 expression in cord and adult blood mononuclear phagocytes.

  1999cited by this paper
• Functional Analysis of the Proximal CCR5 Promoter

  1998cited by this paper
• Interferon-gamma increases expression of chemokine receptors CCR1, CCR3, and CCR5, but not CXCR4 in monocytoid U937 cells.

  1998cited by this paper
• Interferon-γ Increases Expression of Chemokine Receptors CCR1, CCR3, and CCR5, But Not CXCR4 in Monocytoid U937 Cells

  1998cited by this paper
• CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia

  1997cited by this paper
• Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells.

  1995cited by this paper
• Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells

  1995cited by this paper
• Mononuclear phagocytes.

  1989cited by this paper
• Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2 2 DD C T Method

  year unknowncited by this paper

• Mechanisms of transcriptional regulation of CCR5, which is the co-receptor for R5-tropic HIV and is also involved in other disease processes

  2026cites this paper
• Targeting TYROBP to influence the immune microenvironment and osteogenic differentiation of mesenchymal stem cells

  2025cites this paper
• Zinc Oxide-Copper Sulfide Nanozyme Hydrogels for Bone Defect Repair by Modulating the Bone Immune Microenvironment and Promoting Osteogenesis/Angiogenesis.

  2025cites this paper
• Lycium‐Barbarum Polysaccharide‐Loaded Dual‐Crosslinked Rigid Hydrogel Enhances Bone Healing in Diabetic Bone Defects by Scavenging Reactive Oxygen Species

  2025cites this paper
• Targeting chaperone-mediated autophagy to regulate osteoclast activity as a therapeutic strategy for osteoporosis

  2025cites this paper
• The complex association between the immune system and the skeletal system in osteoporosis: A study of single-cell RNA sequencing.

  2024cites this paper
• Effects of circulating inflammatory proteins on osteoporosis and fractures: evidence from genetic correlation and Mendelian randomization study

  2024cites this paper
• MCP‐5 suppresses osteoclast differentiation through Ccr5 upregulation

  2024cites this paper
• Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native A3 adenosine receptor in HL-60 cells

  2024cites this paper
• Morusin regulates the migration of M2 macrophages and GBM cells through the CCL4-CCR5 axis.

  2024cites this paper
• Biomimetic siRNA nanogels for regulating macrophage polarization and promoting osteogenesis

  2024cites this paper
• Causal relationship between circulating levels of cytokines and bone mineral density: A mendelian randomization study.

  2024cites this paper
• Chemokines in the tumor microenvironment: implications for lung cancer and immunotherapy

  2024cites this paper
• Inflammation-related mRNA expression in patients with multiple myeloma undergoing hematopoietic stem cell mobilization.

  2023cites this paper
• A cross‐sectional study comparing the inflammatory profile of menstrual effluent vs. peripheral blood

  2023cites this paper
• Bone microenvironment regulative hydrogels with ROS scavenging and prolonged oxygen-generating for enhancing bone repair

  2023cites this paper
• Transcriptomic Changes toward Osteogenic Differentiation of Mesenchymal Stem Cells on 3D‐Printed GelMA/CNC Hydrogel under Pulsatile Pressure Environment

  2023cites this paper
• Characterization of Chemotaxis-Associated Gene Dysregulation in Myeloid Cell Populations in the Lungs during Lipopolysaccharide-Mediated Acute Lung Injury.

  2023cites this paper
• Leveraging mice with diverse microbial exposures for advances in osteoimmunology

  2023cites this paper
• Identification of key genes and pathways in atherosclerosis using integrated bioinformatics analysis

  2023cites this paper
• Assembling the Puzzle Pieces. Insights for in Vitro Bone Remodeling

  2023cites this paper
• Massively HIV-1-infected macrophages exhibit a severely hampered ability to differentiate into osteoclasts

  2023cites this paper
• Polystyrene micro-/nanoplastics induced hematopoietic damages via the crosstalk of gut microbiota, metabolites, and cytokines.

  2022cites this paper
• Heterochronic parabiosis induces stem cell revitalization and systemic rejuvenation across aged tissues.

  2022cites this paper
• Splenic red pulp macrophages provide a niche for CML stem cells and induce therapy resistance

  2022cites this paper
• Targeting reactive oxygen species in stem cells for bone therapy.

  2021cites this paper
• CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin αvβ3 Axis

  2021cites this paper
• RSPO2 and RANKL signal through LGR4 to regulate osteoclastic premetastatic niche formation and bone metastasis

  2021cites this paper
• Proteomic analysis of aqueous humor in canine primary angle-closure glaucoma in American Cocker Spaniel dogs.

  2021cites this paper
• Inhibitory Effect of Cudratrixanthone U on RANKL-Induced Osteoclast Differentiation and Function in Macrophages and BMM Cells

  2020cites this paper
• Increased Chemokine RANTES in Synovial Fluid and Its Role in Early-stage Degenerative Temporomandibular Joint Disease.

  2020cites this paper
• Receptor and signaling pathway involved in bovine lymphocyte activation by Atractylodis macrocephalae polysaccharides.

  2020cites this paper
• Chemokines in bone-metastatic breast cancer: Therapeutic opportunities.

  2020cites this paper
• Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Drives Activation of Bone Remodelling and Skeletal Metastasis

  2019cites this paper
• Chemokines in Physiological and Pathological Bone Remodeling

  2019cites this paper
• CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation

  2019cites this paper
• The potential risks of C-C chemokine receptor 5-edited babies in bone development

  2019cites this paper
• Neural precursor cell‐expressed, developmentally down‐regulated 4 (NEDD4) regulates hydrogen peroxide‐induced cell proliferation and death through inhibition of Hippo signaling

  2019cites this paper