E-cadherin is important for cell differentiation during osteoclastogenesis

Fiorino, Cara; Harrison, Rene E.

doi:10.1016/j.bone.2016.03.004

Cited by 37 publications

(34 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5C). Although recently a number of studies have focused on the morphologies of fusion partners immediately prior to fusion (Oikawa et al, 2012; Takito and Nakamura, 2012; Takito et al, 2012; Fiorino and Harrison, 2016), knowledge about the molecular composition at these fusion sites is still very scarce. However, considering that syncytin‐1 originates from a retroviral fusion protein it may make sense that it is this fusion route that is affected.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…These analyses are powerful, but are not able to elucidate on the details of individual fusion events leading to this outcome. However, recently analyses of OC fusion in real‐time have been used to identify novel details with regard to the individual fusion partners, their molecular‐ and fusion‐characteristics (Takito and Nakamura, 2012; Takito et al, 2012; Levaot et al, 2015; Soe et al, 2015; Wang et al, 2015; Fiorino and Harrison, 2016). We have recently published a study (Soe et al, 2015), in which we analyzed a large quantity of time‐lapse recordings made over a period of 4 days.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

show abstract

“…Consequently, deletion of this integrin impairs cytoskeletal organisation and the resorbing function of osteoclasts (Faccio et al, 2005;McHugh et al, 2000). In addition, E-cadherin also mediates cell-cell adhesion in osteoclasts and MGCs (Moreno et al, 2007;Fiorino and Harrison, 2016).…”

Section: Macrophage Chemotaxis Adhesion and Cytoskeletal Rearrangementsmentioning

confidence: 99%

Common signalling pathways in macrophage and osteoclast multinucleation

Pereira

Petretto

Gordon

et al. 2018

Journal of Cell Science

169

161

View full text Add to dashboard Cite

Macrophage cell fusion and multinucleation are fundamental processes in the formation of multinucleated giant cells (MGCs) in chronic inflammatory disease and osteoclasts in the regulation of bone mass. However, this basic cell phenomenon is poorly understood despite its pathophysiological relevance. Granulomas containing multinucleated giant cells are seen in a wide variety of complex inflammatory disorders, as well as in infectious diseases. Dysregulation of osteoclastic bone resorption underlies the pathogenesis of osteoporosis and malignant osteolytic bone disease. Recent reports have shown that the formation of multinucleated giant cells and osteoclast fusion display a common molecular signature, suggesting shared genetic determinants. In this Review, we describe the background of cell-cell fusion and the similar origin of macrophages and osteoclasts. We specifically focus on the common pathways involved in osteoclast and MGC fusion. We also highlight potential approaches that could help to unravel the core mechanisms underlying bone and granulomatous disorders in humans.

show abstract

“…Thus far, DC-STAMP and OC-STAMP are the only molecules shown to be expressed by OCps and foreignbody giant cells for their cell fusion (38), making their biologic properties of particular interest in the study field of bone biology. Indeed, several other cell surface molecules, such as meltrin-a, CD47, syncytin-1, and E-cadherin, have been described for their roles in OC fusion, but their expression and activities are not restricted to OCps or giant cells (38)(39)(40)(41)(42). For example, knockdown of OC-STAMP resulted in the inhibition of multinucleated OC formation and decreased expression of genes including transcription factor c-Jun, receptors RANK and c-Fms, TRAF6 signaling molecule, and cell-fusion-related molecule meltrin-a (43).…”

Section: Discussionmentioning

confidence: 99%

OC‐STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up‐regulation of permissive fusogen CD9

Ishii

Ruiz-Torruella²,

Ikeda³

et al. 2018

FASEB j.

View full text Add to dashboard Cite

Cell fusion-mediated formation of multinuclear osteoclasts (OCs) plays a key role in bone resorption. It is reported that 2 unique OC-specific fusogens [ i.e., OC-stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP)], and permissive fusogen CD9, are involved in OC fusion. In contrast to DC-STAMP-knockout (KO) mice, which show the osteopetrotic phenotype, OC-STAMP-KO mice show no difference in systemic bone mineral density. Nonetheless, according to the ligature-induced periodontitis model, significantly lower level of bone resorption was found in OC-STAMP-KO mice compared to WT mice. Anti-OC-STAMP-neutralizing mAb down-modulated in vitro: 1) the emergence of large multinuclear tartrate-resistant acid phosphatase-positive cells, 2) pit formation, and 3) mRNA and protein expression of CD9, but not DC-STAMP, in receptor activator of NF-κB ligand (RANKL)-stimulated OC precursor cells (OCps). While anti-DC-STAMP-mAb also down-regulated RANKL-induced osteoclastogenesis in vitro, it had no effect on CD9 expression. In our mouse model, systemic administration of anti-OC-STAMP-mAb suppressed the expression of CD9 mRNA, but not DC-STAMP mRNA, in periodontal tissue, along with diminished alveolar bone loss and reduced emergence of CD9 OCps and tartrate-resistant acid phosphatase-positive multinuclear OCs. The present study demonstrated that OC-STAMP partners CD9 to promote periodontal bone destruction by up-regulation of fusion during osteoclastogenesis, suggesting that anti-OC-STAMP-mAb may lead to the development of a novel therapeutic regimen for periodontitis.-Ishii, T., Ruiz-Torruella, M., Ikeda, A., Shindo, S., Movila, A., Mawardi, H., Albassam, A., Kayal, R. A., Al-Dharrab, A. A., Egashira, K., Wisitrasameewong, W., Yamamoto, K., Mira, A. I., Sueishi, K., Han, X., Taubman, M. A., Miyamoto, T., Kawai, T. OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9.

show abstract

E-cadherin is important for cell differentiation during osteoclastogenesis

Cited by 37 publications

References 54 publications

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

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

Common signalling pathways in macrophage and osteoclast multinucleation

OC‐STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up‐regulation of permissive fusogen CD9

Contact Info

Product

Resources

About