Contributions of the Measles Virus Nucleocapsid Gene and the SQSTM1/p62P392L Mutation to Paget's Disease

Kurihara, Noriyoshi; Hiruma, Yuko; Yamana, Kei; Michou, Laëtitia; Rousseau, Côme; Morissette, Jean; Galson, Deborah L.; Teramachi, Jumpei; Zhou, Hua; Dempster, David W.; Windle, Jolene J.; Brown, Jacques P.; Roodman, G. David

doi:10.1016/j.cmet.2010.12.002

Cited by 111 publications

(137 citation statements)

References 32 publications

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“…We previously showed that MVNP expression in OCLs induced a pagetic-like phenotype and pagetic-like bone lesions in mice (13,20). In contrast, mice with germline transmission of the mouse equivalent of the most frequent mutation linked to PD, p62 P394L , did not develop pagetic-like bone lesions (12,13).…”

Section: Discussionmentioning

confidence: 99%

“…OCLs from patients with PD express high levels of IL-6 (8), and MVNP expression in OCLs induces high IL-6 expression levels that are essential for the formation of pagetic-like OCLs and bone lesions in MVNP-expressing mice (13). However, it is unknown whether IL-6 increases IGF1 expression, which would in turn increases ephrin B2 levels in MVNP mice.…”

Section: Il-6 Induces Igf1 Expression In Mvnp-expressing Oclsmentioning

confidence: 99%

“…Further, p62-KI mice bred with MVNP mice (p62-KI MVNP mice) develop greater numbers of pagetic-like OCLs and more dramatic bone lesions than do MVNP mice (13). Importantly, loss of IL-6 expression in MVNP mice abrogated both the production of pagetic-like OCLs and increased bone formation in vivo (13).…”

Section: Introductionmentioning

confidence: 99%

“…We previously found that OCLs from 70% of patients with PD express the measles virus nucleocapsid protein (MVNP) gene, and transgenic mice with MVNP targeted to OCLs (MVNP mice) develop OCLs and bone lesions that are characteristic of PD (13). Further, p62-KI mice bred with MVNP mice (p62-KI MVNP mice) develop greater numbers of pagetic-like OCLs and more dramatic bone lesions than do MVNP mice (13).…”

Section: Introductionmentioning

confidence: 99%

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Measles virus nucleocapsid protein increases osteoblast differentiation in Paget’s disease

Teramachi¹,

Nagata²,

Mohammad³

et al. 2016

Journal of Clinical Investigation

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Section: Discussionmentioning

confidence: 99%

Section: Il-6 Induces Igf1 Expression In Mvnp-expressing Oclsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Measles virus nucleocapsid protein increases osteoblast differentiation in Paget’s disease

Teramachi¹,

Nagata²,

Mohammad³

et al. 2016

Journal of Clinical Investigation

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“…Although normal human osteoclasts in the bone contain three to ten nuclei per cell, pagetic osteoclasts contain up to 100 nuclei. Osteoclasts differentiated from human and mouse bone marrow cells overexpressing measles virus nucleocapsid protein (MVNP) gene, a causative gene for Paget's disease, contain more nuclei than the control osteoclasts (Kurihara et al, 2000;Kurihara et al, 2011). Cherubism is a dominantly inherited syndrome characterized by excessive bone resorption in the jaws and accumulation of inflammatory and/or fibrous tissue in the lower face.…”

Section: Introductionmentioning

confidence: 99%

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

Takito

Nakamura

Yoda

et al. 2012

Journal of Cell Science

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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.

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Molecular Genetics of Paget's Disease of Bone

Gennari

Gianfrancesco

Rendina

et al. 2014

Encyclopedia of Life Sciences

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Paget's disease of bone (PDB) is a chronic disorder of bone metabolism, which typically results in enlarged and deformed bones in one or more regions of the skeleton. The aetiology of PDB has remained unknown for several decades, but either environmental or genetic factors have been implicated. The former mainly concern the presence of a slow‐acting viral infection, a condition that may be present for many years before symptoms appear. However, there are also several data supporting a hereditary hypothesis, since in up to 40% of patients the disease may appear in more than one family member. The genetic architecture of PDB is incompletely understood, but recent evidence suggests that the disease may be caused by a combination of rare variants in genes such as SQSTM 1 (detected in up to 50% of familial cases of PDB) and more common variants (i.e. polymorphisms) in genes such as CSF1 , TNFRSF11A , OPTN and TM7SF4 . Key Concepts: Paget's disease of bone (PDB) is a focal disorder of bone metabolism characterised by enlarged and deformed bones in one (monostotic form) or more regions (polyostotic form) of the skeleton. Over the last two decades there have been major advances in our understanding of the genetic basis of the disorder. Mutations in 3 genes have been detected in rare syndromes related to PDB and mutations in SQSTM1 gene have been associated with the classical form of PDB in up to 50% of familial cases. SQSTM1 gene encodes for the p62/sequestosome 1 protein, which acts as a scaffold protein in the NFκB pathway as well as an intermediate protein in the proteosomal degradation of polyubiquitinated proteins. To date the exact molecular mechanisms leading to the development of pagetic lesions in SQSTM1 mutation carriers remain to be defined. Indeed, recent experimental evidence suggests that additional contribution from environmental factors (i.e. a viral infection with paramyxovirus) or other genetic factors (i.e. polymorphisms) may be required to induce the full pagetic phenotype in the presence of SQSTM1 mutation. The genetic cause of PDB in familial cases negative for SQSTM1 mutations remains to be determined in more detail.

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Contributions of the Measles Virus Nucleocapsid Gene and the SQSTM1/p62P392L Mutation to Paget's Disease

Cited by 111 publications

References 32 publications

Measles virus nucleocapsid protein increases osteoblast differentiation in Paget’s disease

Measles virus nucleocapsid protein increases osteoblast differentiation in Paget’s disease

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

Molecular Genetics of Paget's Disease of Bone

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