The role of Mac‐1 (CD11b/CD18) in osteoclast differentiation induced by receptor activator of nuclear factor‐κB ligand

Hayashi, Hidetaka; Nakahama, Ken-ichi; Sato, Takahiro; Tuchiya, Takehiko; Asakawa, Yasuyuki; Maemura, T.; Tanaka, Masanobu; Morita, Mineto; Morita, Ikuo

doi:10.1016/j.febslet.2008.08.023

Cited by 41 publications

(45 citation statements)

References 29 publications

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“…Recently, it is reported that reduction of activity of CD11b by siRNA and neutralizing antibody inhibited CD11b+ mononuclear cells osteoclastogenesis by M-CSF and RANKL [Hayashi et al, 2008]. Hence, CD11b+ is thought to be a marker of osteoclast precursors.…”

Section: Discussionmentioning

confidence: 99%

“…CD11b/CD18 is also known as Mac-1/C R3, and α M β 2 -integrin and is expressed in human monocytes, macrophages, neutrophils and eosinophils [Murdoch et al, 2008]. Hayashi et al demonstrated that CD11/CD18 is required for nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation [Hayashi et al, 2008].RANKL induces osteoclast formation and activation in the presence of macrophage colony stimulating factor (M-CSF) through NFATc-1 and MMP9 activation [Boyce and Xing, 2008;Del Fattore et al, 2008;Takayanagi, 2005]. Furthermore, IL-6 and IL-8 are known to be highly expressed in prostate cancer metastatic sites [Lu et al, 2007].…”

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confidence: 99%

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Prostate Cancer Promotes Cd11b Positive Cells to Differentiate Into Osteoclasts

Mizutani¹,

Sud²,

Pienta³

2009

Journal of Urology

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Bone is the preferred site of prostate cancer metastasis, contributing to the morbidity and mortality of this disease. A key step in the successful establishment of prostate cancer bone metastases is activation of osteoclasts with subsequent bone resorption causing the release of several growth factors from the bone matrix. CD11b+ cells in bone marrow are enriched for osteoclast precursors. Conditioned media from prostate cancer PC-3 cells induces CD11b+ cells from human peripheral blood to differentiate into functional osteoclasts with subsequent bone resorption. Analysis of PC-3 conditioned media revealed high amounts of IL-6 and IL-8. CD11b+ cells were cultured with M-CSF and RANKL, IL-6, IL-8 and CCL2, alone or in combination. All of these conditions induced osteoclast fusion, but cells cultured with M-CSF, IL-6, IL-8 and CCL2 were capable of limited bone resorption. Co-incubation with IL-6 and IL-8 and the RANK inhibitor, RANK-Fc, failed to inhibit osteoclast fusion and bone resorption, suggesting a potential RANKL-independent mechanism of functional osteoclast formation. This study demonstrates that functional osteoclasts can be derived from CD11b+ cells derived from human PBMCs. Prostate cancer cells secrete factors, including IL-6 and IL-8, that play an important role in osteoclast fusion by a RANKLindependent mechanism. KeywordsOsteoclast; CD11b; Prostate Cancer; RANKL; IL-6; IL-8; CCL2Prostate cancer is the most commonly diagnosed malignancy in US men [Walczak and Carducci, 2007]. Advanced prostate cancer is first treated through chemical or surgical castration because a large percentage of the cancer cells are androgen dependent. The large majority of patients, however, relapse within a few years of treatment because of the emergence of a castration resistant clone of cancer cells. Castration independent prostate cancer is an incurable disease with little effective therapy and there is a great need for novel therapeutic strategies that target the molecular basis of castration-independent, chemoresistant prostate cancer [Isaacs, 2005]. Previous studies have demonstrated that 83%-90% of men had evidence of bone metastasis when they died of prostate cancer Kingsley et al., 2007;Loberg et al., 2005]. Bone is the preferred metastasis site of advanced prostate cancer, and in many patients, the only clinically evident site of metastasis at the time of death . There is a great need of novel therapeutic strategies that target the molecular basis of advanced prostate cancer -bone interactions. A NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript key step in the successful establishment of prostate cancer bone metastases is osteoclast formation and bone resorption followed by the release of several growth factors from the bone matrix that promotes tumor growth . The mechanisms by which prostate cancer cells promote osteoclast formation and bone resorption remain unclear.Previous reports suggested that RANKL, Interleukin-6 (IL-6), Interleukin-8 (IL-8) and C-C chemokine ligand 2 (MC...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Prostate Cancer Promotes Cd11b Positive Cells to Differentiate Into Osteoclasts

Mizutani¹,

Sud²,

Pienta³

2009

Journal of Urology

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“…Our previous study showed that expression of the cell surface receptor macrophage antigen 1 (Mac-1, CD11b/ CD18) might accelerate differentiation into osteoclasts via modulation of pre-OC cell-cell communication [56]. We demonstrated a positive relationship between CD11b expression on pre-OCs and osteoclastogenesis, an inhibitory effect of a CD11b neutralizing antibody on osteoclastogenesis, and an inhibitory effect of knockdown of CD11b on osteoclastogenesis using a macrophage cell line (RAW264.7) and bone marrow-derived macrophages stimulated with RANKL.…”

Section: Extravasation Of Osteoclast Precursors (Endothelial Cell-ostmentioning

confidence: 99%

Cellular communications in bone homeostasis and repair

Nakahama

2010

Cell. Mol. Life Sci.

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125

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Cellular communication between the bone component cells osteoblasts, osteocytes and (pre-)osteoclasts is essential for bone remodeling which maintains bone integrity. As in the remodeling of other organs, cell death is a trigger for remodeling of bone. During the systematic process of bone remodeling, direct or indirect cell-cell communication is indispensable. Thus, osteoblasts induce migration and differentiation of preosteoclasts, which is followed by bone resorption (by mature multinuclear osteoclasts). After completion of bone resorption, apoptosis of mature osteoclasts and differentiation of osteoblasts are initiated. At this time, the osteoblasts do not support osteoclast differentiation but do support bone formation. Finally, osteoblasts differentiate to osteocytes in bone or to bone lining cells on bone surfaces. In this way, old bone areas are regenerated as new bone. In this review the role of cell-cell communication in bone remodeling is discussed.

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“…Furthermore, we showed that CS-E and heparin bound to RAW264 cells (Table 4). Therefore, one of the mechanisms is assumed to be that in which these sulfated GAGs existed on osteoblast cell surface or bone matrix including HA or fibronectin bind to preosteoclasts cell surface molecules such as integrins 24,26,27) , and inhibit osteoclast differentiation. Moreover, binding of CS-E to fibronectin have a possibility to cause the inhibition of fibronectin-integrin interaction.…”

Section: Control Cs-c Cs-e Hepmentioning

confidence: 99%

Effect of chondroitin sulfate-E on the osteoclastic differentiation of RAW264 cells

Miyazaki

Miyauchi²,

Tawada³

et al. 2010

Dent. Mater. J.

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The present study was designed to investigate whether chondroitin sulfate (CS)-E, a CS structural isomer variant, alter the differentiation of macrophage cell line RAW264 cells to osteoclast-like cells. CS-B, CS-E, low molecular weight CS-E, synthetic chondroitin polysulfate (CPS) and heparin significantly inhibited the formation of tartrate-resistant acid phosphatase-positive multinuclear cells and pit formation on calcium phosphate (CaP)-coated plates. CS-E pre-coated on the CaP plate also inhibited pit formation. Digestion of CS on the cell surface by chondroitinase showed no effect on the osteoclastic differentiation of RAW264 cells whereas inhibitory effect on the differentiation of osteoblastic cell line MC3T3-E1. On the other hand, exogenously added fluoresceinlabeled CS-E directory bound to fibronectin and RAW264 cells. These results suggest that CS-E structure on the surface of osteoblasts or bone matrix binds to cell adhesion molecule such as integrin on the pre-osteoclastic cells and inhibits the differentiation into osteoclasts. CS-E may have a potential in treating bone defect if combined with CaP materials.

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The role of Mac‐1 (CD11b/CD18) in osteoclast differentiation induced by receptor activator of nuclear factor‐κB ligand

Cited by 41 publications

References 29 publications

Prostate Cancer Promotes Cd11b Positive Cells to Differentiate Into Osteoclasts

Prostate Cancer Promotes Cd11b Positive Cells to Differentiate Into Osteoclasts

Cellular communications in bone homeostasis and repair

Effect of chondroitin sulfate-E on the osteoclastic differentiation of RAW264 cells

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