Vascular expression of the chemokine CX3CL1 promotes osteoclast recruitment and exacerbates bone resorption in an irradiated murine model

Han, Ki Hoon; Ryu, Jae Won; Lim, Kyung-Eun; Lee, Soo-Han; Kim, Yuna; Hwang, Chang Sun; Choi, Je‐Yong; Han, Kyoung-Sik

doi:10.1016/j.bone.2013.12.032

Cited by 38 publications

(25 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The chemokine CX3CL1 can recruit osteoclasts which are formed by fusion and differentiation of monocytes (114). This might have clinical relevance for osteolytic tumors.…”

Section: Cytokines and Chemokinesmentioning

confidence: 99%

Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

Diegeler

Hellweg

2017

Front. Immunol.

View full text Add to dashboard Cite

Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response. In recent years, much progress has been achieved in the understanding of basic interactions between the irradiated tumor and the immune system. Here, direct and indirect effects of radiation on immune cells have to be considered. Lymphocytes for example are known to be highly radiosensitive. One important factor in indirect interactions is the radiation-induced bystander effect which can be initiated in unexposed cells by expression of cytokines of the irradiated cells and by direct exchange of molecules via gap junctions. In this review, we summarize the current knowledge about the indirect effects observed after exposure to different radiation qualities. The different immune cell populations important for the tumor immune response are natural killer cells, dendritic cells, and CD8+ cytotoxic T-cells. In vitro and in vivo studies have revealed the modulation of their functions due to ionizing radiation exposure of tumor cells. After radiation exposure, cytokines are produced by exposed tumor and immune cells and a modulated expression profile has also been observed in bystander immune cells. Release of damage-associated molecular patterns by irradiated tumor cells is another factor in immune activation. In conclusion, both immune-activating and -suppressing effects can occur. Enhancing or inhibiting these effects, respectively, could contribute to modified tumor cell killing after radiotherapy.

show abstract

“…The chemokine CX3CL1 can recruit osteoclasts which are formed by fusion and differentiation of monocytes (114). This might have clinical relevance for osteolytic tumors.…”

Section: Cytokines and Chemokinesmentioning

confidence: 99%

Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

Diegeler

Hellweg

2017

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Additionally, Fu, Pang, Xu, & Wu, observed that EPCs promote survival, migration, and differentiation of osteoclast precursors by producing VEGF A, SDF‐1, and transforming growth factor β1 (TGF‐β1) (Fu et al, ; Pang et al, ), which supports the role of SDF‐1 in the crosstalk between EPCs and osteoclasts. Meanwhile, it has been reported that irradiation elevated another chemokine CX3CL1 by vascular endothelium and stimulated osteoclastogenesis (Han et al, ). But, the precise mechanism should be elucidated after further research.…”

Section: Discussionmentioning

confidence: 99%

Suppressing angiogenesis regulates the irradiation‐induced stimulation on osteoclastogenesis in vitro

Tong

Zhu

Wang

et al. 2017

Journal Cellular Physiology

View full text Add to dashboard Cite

Ionizing radiation-induced bone loss is a potential health concern in radiotherapy, occupational exposure, and astronauts. Although impaired bone vasculature and reduced proliferation of bone-forming osteoblasts has been implicated in this process, it has not been clearly characterized that whether radiation affects the growth of bone-resorbing osteoclasts. The molecular crosstalk between different cell populations in the skeletal system has not yet been elucidated in detail, especially between the increased bone resorption at early stage of post-irradiation and bone marrow-derived endothelial progenitor cells (BM-EPCs). In order to further understand the mechanisms involved in radiation-induced bone loss at the cellular level, we assessed the effects of irradiation on angiogenesis of BM-EPCs and osteoclastogenesis of receptor activator for nuclear factor-κB ligand (RANKL)-stimulated RAW 264.7 cells and crosstalk between these cell populations. We herein found significantly dysfunction of BM-EPCs in response to irradiation at a dose of 2 Gy, including inhibited proliferation, migration, tube-forming abilities, and downregulated expression of pro-angiogenesis vascular endothelial growth factors A (VEGF A). Meanwhile, we observed that irradiation promoted osteoclastogenesis of RANKL-stimulated RAW 264.7 cells directly or indirectly. These results provide quantitative evidences of irradiation induced osteoclastogenesis at a cellular level, and strongly suggest the involvement of osteoclastogenesis, angiogenesis and crosstalk between bone marrow cells in the radiation-induced bone loss. This study may provide new insights for the early diagnosis and intervention of bone loss post-irradiation.

show abstract

“…Interestingly, CX 3 CL1 is produced by mouse osteoblasts [151] and CX 3 CR1 deficient mice have a reduction in osteoclasts that results in a mild increase in bone mass [152]. Furthermore, functional inhibition of CX 3 CR1 signaling provided protection from bone loss induced by irradiation [153], perhaps by disrupting CX 3 CR1-mediated migration and retention in the bone marrow [136]. In summary, while these studies suggest that synergy between multiple chemokine receptors controls osteoclastogenesis, only EBI2 was shown to be directly required for osteoclast precursor positioning in bone endosteal niches (Figure 1).…”

Section: Osteoclast Differentiation Under Homeostasismentioning

confidence: 99%

“…Blockade of CX 3 CR1 in a murine model decreased the recruitment of monocytic cells to synovial tissues and decreased disease incidence and severity [82]. CX 3 CL1 is elevated in RA patients compared to OA patients [81,80] and CX 3 CL1 has been shown to be upregulated in mouse bone marrow endothelial cells in inflammatory conditions, such as full body irradiation [153]. …”

Section: Recruitment Of Osteoclast Precursors In Ramentioning

confidence: 99%

Inflammatory Cell Migration in Rheumatoid Arthritis: A Comprehensive Review

Nevius

Gomes

Pereira

2015

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects the joints. Self-reactive B and T lymphocytes cooperate to promote antibody responses against self proteins and are major drivers of disease. T lymphocytes also promote RA independently of B lymphocytes mainly through the production of key inflammatory cytokines, such as IL-17, that promote pathology. While the innate signals that initiate self-reactive adaptive immune responses are poorly understood, the disease is predominantly caused by inflammatory cellular infiltration and accumulation in articular tissues, and by bone erosions driven by bone-resorbing osteoclasts. Osteoclasts are giant multinucleated cells formed by the fusion of multiple myeloid cells that require short-range signals, such as the cytokines MCSF and RANKL, for undergoing differentiation. The recruitment and positioning of osteoclast precursors to sites of osteoclast differentiation by chemoattractants is an important point of control for osteoclastogenesis and bone resorption. Recently, the GPCR EBI2 and its oxysterol ligand 7a, 25 dihydroxycholesterol were identified as important regulators of osteoclast precursor positioning in proximity to bone surfaces, and of osteoclast differentiation under homeostasis. In chronic inflammatory diseases like RA, osteoclast differentiation is also driven by inflammatory cytokines such as TNFa and IL-1, and can occur independently of RANKL. Finally, there is growing evidence that the chemotactic signals guiding osteoclast precursors to inflamed articular sites contribute to disease and are of great interest. Furthering our understanding of the complex osteoimmune cell interactions should provide new avenues of therapeutic intervention for RA.

show abstract

Vascular expression of the chemokine CX3CL1 promotes osteoclast recruitment and exacerbates bone resorption in an irradiated murine model

Cited by 38 publications

References 59 publications

Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities

Suppressing angiogenesis regulates the irradiation‐induced stimulation on osteoclastogenesis in vitro

Inflammatory Cell Migration in Rheumatoid Arthritis: A Comprehensive Review

Contact Info

Product

Resources

About