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

Lee, Dabin; Shin, Kyung-Ju; Kim, Dong Wook; Yoon, Kyung Hoon; Choi, Youngjin; Lee, Bom Nae Rin; Cho, Je‐Yoel

doi:10.1038/s41419-018-0562-5

Cited by 34 publications

(18 citation statements)

References 49 publications

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“…Competitive transplantation studies with HSCs with either CCL5 -deficient or CCL5 -replete cells did not demonstrate differences in the levels of total engraftment (Ergen et al., 2012). Since ligands for CCR5 include CCL3 and CCL4, it is possible that these ligands could provide functional redundancy for CCR5 signaling when CCL5 alone is depleted (Lee et al., 2018, Menten et al., 2002). For these reasons, we sought to genetically abolish CCR5 signaling by using Ccr5 -deficient mice.…”

Section: Discussionmentioning

confidence: 99%

CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation

Piryani

Kam

et al. 2019

Stem Cell Reports

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Hematopoietic stem and progenitor cells (HSPCs) depend on regulatory cytokines from the marrow microenvironment. From an unbiased cytokine screen of murine marrow supernatants, we identified CC motif chemokine ligand 5 (CCL5) as an endothelial cell-secreted hematopoietic growth factor. Following treatment with CCL5, hematopoietic regeneration is accelerated and survival is prolonged after radiation. In mice with deletion of Ccr5, hematopoietic regeneration is delayed compared to control mice. Deletion of Ccr5 specifically in hematopoietic cells was sufficient to delay regeneration, while the deletion of Ccr5 in stromal/endothelial cells was not. Mechanistically, CCL5 promotes hematopoietic cell cycling and cell survival. Like murine hematopoietic cells, human hematopoietic cells (cord blood, healthy marrow, and peripheral blood) increase CCR5 expression after radiation exposure to promote cell survival. These data establish that CCL5 and CCR5 signaling play critical roles in hematopoietic regeneration and could serve as therapeutic targets to shorten the duration of myelosuppression.

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Section: Discussionmentioning

confidence: 99%

CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation

Piryani

Kam

et al. 2019

Stem Cell Reports

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“…In line with this observation, another study reported that treatment of mouse osteoclast progenitor cells with CCL4 did not influence RANKL-mediated osteoclastogenesis. However, the decrease in expression of its receptor CCR5 during osteoclast formation, was shown to be essential for osteoclastogenesis (106).…”

Section: Influence Of Cc-chemokines On Bone Remodeling In Health and mentioning

confidence: 99%

Chemokines in Physiological and Pathological Bone Remodeling

2019

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The bone matrix is constantly remodeled by bone-resorbing osteoclasts and bone-forming osteoblasts. These two cell types are fundamentally different in terms of progenitor cells, mode of action and regulation by specific molecules, acting either systemically or locally. Importantly, there is increasing evidence for an impact of cell types or molecules of the adaptive and innate immune system on bone remodeling. Understanding these influences is the major goal of a novel research area termed osteoimmunology, which is of key relevance in the context of inflammation-induced bone loss, skeletal metastases, and diseases of impaired bone remodeling, such as osteoporosis. This review article aims at summarizing the current knowledge on one particular aspect of osteoimmunology, namely the impact of chemokines on skeletal cells in order to regulate bone remodeling under physiological and pathological conditions. Chemokines have key roles in the adaptive immune system by controlling migration, localization, and function of immune cells during inflammation. The vast majority of chemokines are divided into two subgroups based on the pattern of cysteine residues. More specifically, there are 27 known C-C-chemokines, binding to 10 different C-C receptors, and 17 known C-X-C-chemokines binding to seven different C-X-C receptors. Three additional chemokines do not fall into this category, and only one of them, i.e., CX3CL1, has been shown to influence bone remodeling cell types. There is a large amount of published studies demonstrating specific effects of certain chemokines on differentiation and function of osteoclasts and/or osteoblasts. Chemokine signaling by skeletal cells or by other cells of the bone marrow niche regulates bone formation and resorption through autocrine and paracrine mechanisms. In vivo evidence from mouse deficiency models strongly supports the role of certain chemokine signaling pathways in bone remodeling. We will summarize these data in the present review with a special focus on the most established subsets of chemokines. In combination with the other review articles of this issue, the knowledge presented here confirms that there is a physiologically relevant crosstalk between the innate immune system and bone remodeling cell types, whose molecular understanding is of high clinical relevance.

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“…In contrast to MCP-1, which fully reversed GM-CSF repression of osteoclast formation, RANTES recovered multinuclear cell formation, but the cells lacked the ability to resorb bone [27••]. Consistent with the expression of its receptor, and another potential receptor of MCP-1, CCR4 in human osteoclast precursors [35], CCL4 (also known as MIP1b) does not enhance osteoclast formation but was found to be chemotactic to osteoclast precursors [37]. Therefore, several chemokines of the CC family (MCP-1, CCL3 and CCL5) are produced in differentiating human osteoclasts and all have similar actions in promoting osteoclast fusion and survival.…”

Section: The Role Of Mcp-1 In Bone Remodellingmentioning

confidence: 95%

Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Drives Activation of Bone Remodelling and Skeletal Metastasis

Mulholland

Forwood

Morrison

2019

Curr Osteoporos Rep

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Purpose of Review The purpose of this review is to explore the role of monocyte chemoattractant protein-1 (MCP-1 or CCL2) in the processes that underpin bone remodelling, particularly the action of osteoblasts and osteoclasts, and its role in the development and metastasis of cancers that target the bone. Recent Findings MCP-1 is a key mediator of osteoclastogenesis, being the highest induced gene during intermittent treatment with parathyroid hormone (iPTH), but also regulates catabolic effects of continuous PTH on bone including monocyte and macrophage recruitment, osteoclast formation and bone resorption. In concert with PTH-related protein (PTHrP), MCP-1 mediates the interaction between tumour-derived factors and host-derived chemokines to promote skeletal metastasis. In breast and prostate cancers, an osteolytic cascade is driven by tumour cell-derived PTHrP that upregulates MCP-1 in osteoblastic cells. This relationship between PTHrP and osteoblastic expression of MCP-1 may drive the colonisation of disseminated breast cancer cells in the bone. Summary There is mounting evidence to suggest a pivotal role of MCP-1 in many diseases and an important role in the establishment of comorbidities. Coupled with its role in bone remodelling and the regulation of bone turnover, there is the potential for pathological relationships between bone disorders and bone-related cancers driven by MCP-1. MCP-1's role in bone remodelling and bone-related cancers highlights its potential as a novel anti-resorptive and anti-metastatic target. Keywords MCP-1 or CCL-2. Breast cancer. Osteoclast. Bone remodelling. Metastasis This article is part of the Topical Collection on Skeletal Biology and Regulation

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

Cited by 34 publications

References 49 publications

CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation

CCR5 Signaling Promotes Murine and Human Hematopoietic Regeneration following Ionizing Radiation

Chemokines in Physiological and Pathological Bone Remodeling

Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Drives Activation of Bone Remodelling and Skeletal Metastasis

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