The role of cadherin in the generation of multinucleated osteoclasts from mononuclear precursors in murine marrow.

Mbalaviele, Gabriel; Chen, Hong; Boyce, Brendan F.; Mundy, Gregory R.; Yoneda, Toshiyuki

doi:10.1172/jci117979

Cited by 154 publications

(119 citation statements)

References 35 publications

(28 reference statements)

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…This coincides with the results that plating cell density affects the size and morphology of in-vitrodifferentiated osteoclasts (Gardner, 2007). A cell-cell adhesion molecule E-cadherin is reported to be involved in the fusion of mononuclear precursor cells during osteoclastogenesis (Mbalaviele et al, 1995). It is known that reorganization of the actin cytoskeleton is needed for the recruitment of E-cadherin at the cell contact site (Cavey and Lecuit, 2009).…”

Section: Introductionsupporting

confidence: 85%

The transient appearance of zipper-like actin superstructures during the fusion of osteoclasts

Takito

Nakamura

Yoda

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

SummaryMultinucleated osteoclasts are responsible for bone resorption. Hypermultinucleated osteoclasts are often observed in some bone-related diseases such as Paget's disease and cherubism. The cellular mechanics controlling the size of osteoclasts is poorly understood. We introduced EGFP-actin into RAW 264.7 cells to monitor actin dynamics during osteoclast differentiation. Before their terminal differentiation into osteoclasts, syncytia displayed two main types of actin assembly, podosome clusters and clusters of zipper-like structures. The zipper-like structures morphologically resembled the adhesion zippers found at the initial stage of cell-cell adhesion in keratinocytes. In the zipper-like structure, Arp3 and cortactin overlapped with the distribution of dense F-actin, whereas integrin b3, paxillin and vinculin were localized to the periphery of the structure. The structure was negative for WGA-lectin staining and biotin labeling. The zipper-like structure broke down and transformed into a large actin ring, called a podosome belt. Syncytia containing clusters of zipper-like structures had more nuclei than those with podosome clusters. Differentiated osteoclasts with a podosome belt also formed the zipper-like structure at the cell contact site during cell fusion. The breakdown of the cell contact site resulted in the fusion of the podosome belts following plasma membrane fusion. Additionally, osteoclasts in mouse calvariae formed the zipper-like structure in the sealing zone. Therefore, we propose that the zipper-like actin superstructures might be involved in cell-cell interaction to achieve efficient multinucleation of osteoclasts. Understanding of the zipper-like structure might lead to selective therapeutics for bone diseases caused by hypermultinucleated osteoclasts.

show abstract

Section: Introductionsupporting

confidence: 85%

The transient appearance of zipper-like actin superstructures during the fusion of osteoclasts

Takito

Nakamura

Yoda

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…2D), indicating that OC-STAMP is required for osteoclast fusion independent of DC-STAMP. Other molecules reportedly involved in osteoclast cell-cell fusion, such as E-Cadherin and ATP6v0d2, (14,21) were equally expressed in OC-STAMP-deficient compared to WT osteoclasts (Fig. 2E), supporting the idea that OC-STAMP is required for osteoclast fusion rather than as a modulator of expression of fusion-related molecules.…”

Section: Oc-stamp Is Required For Osteoclast Cell-cell Fusionsupporting

confidence: 56%

“…(13) Therefore, although the functions of osteoclasts and FBGCs differ, they express common molecules, such as DC-STAMP, that function in cell-cell fusion. (3) To date, various molecules have been identified that regulate fusion of osteoclasts or macrophages, including DC-STAMP, ATP6v0d2, CD47, CD44, CD9, CD81, MFR, E-cadherin, and meltrin-a (3,(14)(15)(16)(17)(18)(19)(20)(21) ATP6v0d2-deficient mice show significant reductions in fusion of either cell type. (21) DC-STAMP-deficient osteoclasts or FBGCs show a complete lack of cell-cell fusion, a function specific for macrophage lineage fusion, since fertilization and myotube formation is normal in DC-STAMP-deficient mice.…”

Section: Introductionmentioning

confidence: 99%

Osteoclast stimulatory transmembrane protein and dendritic cell–specific transmembrane protein cooperatively modulate cell–cell fusion to form osteoclasts and foreign body giant cells

Miyamoto

Suzuki

Miyauchi

et al. 2012

Journal of Bone and Mineral Research

144

129

View full text Add to dashboard Cite

Cell-cell fusion is a dynamic phenomenon promoting cytoskeletal reorganization and phenotypic changes. To characterize factors essential for fusion of macrophage lineage cells, we identified the multitransmembrane protein, osteoclast stimulatory transmembrane protein (OC-STAMP), and analyzed its function. OC-STAMP-deficient mice exhibited a complete lack of cell-cell fusion of osteoclasts and foreign body giant cells (FBGCs), both of which are macrophage-lineage multinuclear cells, although expression of dendritic cell specific transmembrane protein (DC-STAMP), which is also essential for osteoclast/FBGC fusion, was normal. Crossing OC-STAMP-overexpressing transgenic mice with OC-STAMP-deficient mice restored inhibited osteoclast and FBGC cell-cell fusion seen in OC-STAMP-deficient mice. Thus, fusogenic mechanisms in macrophage-lineage cells are regulated via OC-STAMP and DC-STAMP. ß

show abstract

“…The most prominent of these is DC‐STAMP (dendritic cell‐specific transmembrane protein) (Kukita et al, 2004; Yagi et al, 2005; Iwasaki et al, 2008; Mensah et al, 2010; Chiu et al, 2012; Chiu and Ritchlin, 2016), which has been identified as one of the most essential single factors supporting both differentiation and fusion. However, also other factors such as CD47 (Han et al, 2000; Lundberg et al, 2007; Maile et al, 2011; Koskinen et al, 2013; Hobolt‐Pedersen et al, 2014), syncytin‐1 (Soe et al, 2011), OC‐STAMP (osteoclast stimulatory transmembrane protein) (Miyamoto et al, 2012; Witwicka et al, 2015), dynamin (Shin et al, 2014; Verma et al, 2014), Pin1 (peptidyl‐prolyl cis‐trans isomerase NIMA‐interacting 1) (Islam et al, 2014; Cho et al, 2015), and e‐cadherin (Mbalaviele et al, 1995; Fiorino and Harrison, 2016) are involved in OC fusion, but it is important to stress that this list is not exhaustive. In order to identify the role of these factors , a series of molecular techniques, and cellular model systems have been employed, which in general are evaluated through end‐point measurements by counting the number of multi‐nucleated OCs, number of nuclei per OC, resorptive activity, and so forth at the end of the incubation period.…”

mentioning

confidence: 99%

Osteoclast Fusion: Time‐Lapse Reveals Involvement of CD47 and Syncytin‐1 at Different Stages of Nuclearity

Møller

Delaissé

Søe

2016

Journal Cellular Physiology

View full text Add to dashboard Cite

Investigations addressing the molecular keys of osteoclast fusion are primarily based on end‐point analyses. No matter if investigations are performed in vivo or in vitro the impact of a given factor is predominantly analyzed by counting the number of multi‐nucleated cells, the number of nuclei per multinucleated cell or TRAcP activity. But end‐point analyses do not show how the fusion came about. This would not be a problem if fusion of osteoclasts was a random process and occurred by the same molecular mechanism from beginning to end. However, we and others have in the recent period published data suggesting that fusion partners may specifically select each other and that heterogeneity between the partners seems to play a role. Therefore, we set out to directly test the hypothesis that fusion factors have a heterogenic involvement at different stages of nuclearity. Therefore, we have analyzed individual fusion events using time‐lapse and antagonists of CD47 and syncytin‐1. All time‐lapse recordings have been studied by two independent observers. A total of 1808 fusion events were analyzed. The present study shows that CD47 and syncytin‐1 have different roles in osteoclast fusion depending on the nuclearity of fusion partners. While CD47 promotes cell fusions involving mono‐nucleated pre‐osteoclasts, syncytin‐1 promotes fusion of two multi‐nucleated osteoclasts, but also reduces the number of fusions between mono‐nucleated pre‐osteoclasts. Furthermore, CD47 seems to mediate fusion mostly through broad contact surfaces between the partners’ cell membrane while syncytin‐1 mediate fusion through phagocytic‐cup like structure. J. Cell. Physiol. 232: 1396–1403, 2017. © 2016 Wiley Periodicals, Inc.

show abstract

The role of cadherin in the generation of multinucleated osteoclasts from mononuclear precursors in murine marrow.

Cited by 154 publications

References 35 publications

The transient appearance of zipper-like actin superstructures during the fusion of osteoclasts

The transient appearance of zipper-like actin superstructures during the fusion of osteoclasts

Osteoclast stimulatory transmembrane protein and dendritic cell–specific transmembrane protein cooperatively modulate cell–cell fusion to form osteoclasts and foreign body giant cells

Osteoclast Fusion: Time‐Lapse Reveals Involvement of CD47 and Syncytin‐1 at Different Stages of Nuclearity

Contact Info

Product

Resources

About