Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62P392L mutation to paget's disease

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

doi:10.1016/j.cmet.2010.12.002

Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62^P392L mutation to paget's disease

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

Research output: Contribution to journal › Article › peer-review

97 Citations (Scopus)

Abstract

Paget's disease (PD) is characterized by abnormal osteoclasts (OCL) that secrete high IL-6 levels and induce exuberant bone formation. Because measles virus nucleocapsid gene (MVNP) and the p62^P392L mutation are implicated in PD, marrows from 12 PD patients harboring p62^P392L and eight normals were tested for MVNP expression and pagetic OCL formation. Eight out of twelve patients expressed MVNP and formed pagetic OCL in vitro, which were inhibited by antisense-MVNP. Four out of twelve patients lacked MVNP and formed normal OCL that were hyperresponsive to RANKL but unaffected by antisense-MVNP. Similarly, mice expressing only p62^P394L formed normal OCL, while mice expressing MVNP in OCL, with or without p62 ^P394L, developed pagetic OCL and expressed high IL-6 levels dependent on p38MAPK activation. IL-6 deficiency in MVNP mice abrogated pagetic OCL development in vitro. Mice coexpressing MVNP and p62^P394L developed dramatic Paget's-like bone lesions. These results suggest that p62 ^P394L and IL-6 induction by MVNP play key roles in PD.

Original language	English
Pages (from-to)	23-34
Number of pages	12
Journal	Cell Metabolism
Volume	13
Issue number	1
DOIs	https://doi.org/10.1016/j.cmet.2010.12.002
Publication status	Published - Jan 5 2011
Externally published	Yes

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cmet.2010.12.002

Cite this

Kurihara, N., Hiruma, Y., Yamana, K., Michou, L., Rousseau, C., Morissette, J., Galson, D. L., Teramachi, J., Zhou, H., Dempster, D. W., Windle, J. J., Brown, J. P., & Roodman, G. D. (2011). Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62^P392L mutation to paget's disease. Cell Metabolism, 13(1), 23-34. https://doi.org/10.1016/j.cmet.2010.12.002

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title = "Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62P392L mutation to paget's disease",

abstract = "Paget's disease (PD) is characterized by abnormal osteoclasts (OCL) that secrete high IL-6 levels and induce exuberant bone formation. Because measles virus nucleocapsid gene (MVNP) and the p62P392L mutation are implicated in PD, marrows from 12 PD patients harboring p62P392L and eight normals were tested for MVNP expression and pagetic OCL formation. Eight out of twelve patients expressed MVNP and formed pagetic OCL in vitro, which were inhibited by antisense-MVNP. Four out of twelve patients lacked MVNP and formed normal OCL that were hyperresponsive to RANKL but unaffected by antisense-MVNP. Similarly, mice expressing only p62P394L formed normal OCL, while mice expressing MVNP in OCL, with or without p62 P394L, developed pagetic OCL and expressed high IL-6 levels dependent on p38MAPK activation. IL-6 deficiency in MVNP mice abrogated pagetic OCL development in vitro. Mice coexpressing MVNP and p62P394L developed dramatic Paget's-like bone lesions. These results suggest that p62 P394L and IL-6 induction by MVNP play key roles in PD.",

author = "Noriyoshi Kurihara and Yuko Hiruma and Kei Yamana and La{\"e}titia Michou and C{\^o}me Rousseau and Jean Morissette and Galson, {Deborah L.} and Jumpei Teramachi and Hua Zhou and Dempster, {David W.} and Windle, {Jolene J.} and Brown, {Jacques P.} and Roodman, {G. David}",

note = "Funding Information: We thank Dr. Fujinami, Ph.D., University of Utah, for providing the AS-MVNP construct, and Donna Gaspich for preparing the manuscript. We also thank all patients who participated in this study, and Danielle Poulin for her outstanding support in clinical data collection and analysis. We thank Dr. Ramesh Ramakrishnan for assistance with statistical analyses. The research was funded by grant PO1-AR049363 (G.D.R.), R01 AR057308 (G.D.R.), R01 AR057310 (D.L.G.), and RO1 AR053537 (J.J.W.) from NIAMS, NIH/NCRR/CTSA Grant UL1 RR024153 and NIH/NCRR/GCRC Grant M01 RR000056, and by a grant from the Paget's Foundation. The materials are the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System, Research and Development, and the VCU Transgenic/Knockout Mouse Core, supported in part by the Massey Cancer Center Support Grant P30 CA016059. J.P.B. reports having served as a consultant to Amgen, Sanofi-Aventis, Warner-Chilcott, Merck, E. Lily, Novartis, Servier. G.D.R. reports having served as a consultant to Amgen, Novartis, Celgene, and Millennium and received grant support from Novartis as well. ",

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T1 - Contributions of the measles virus nucleocapsid gene and the SQSTM1/p62P392L mutation to paget's disease

AU - Kurihara, Noriyoshi

AU - Hiruma, Yuko

AU - Yamana, Kei

AU - Michou, Laëtitia

AU - Rousseau, Côme

AU - Morissette, Jean

AU - Galson, Deborah L.

AU - Teramachi, Jumpei

AU - Zhou, Hua

AU - Dempster, David W.

AU - Windle, Jolene J.

AU - Brown, Jacques P.

AU - Roodman, G. David

N1 - Funding Information: We thank Dr. Fujinami, Ph.D., University of Utah, for providing the AS-MVNP construct, and Donna Gaspich for preparing the manuscript. We also thank all patients who participated in this study, and Danielle Poulin for her outstanding support in clinical data collection and analysis. We thank Dr. Ramesh Ramakrishnan for assistance with statistical analyses. The research was funded by grant PO1-AR049363 (G.D.R.), R01 AR057308 (G.D.R.), R01 AR057310 (D.L.G.), and RO1 AR053537 (J.J.W.) from NIAMS, NIH/NCRR/CTSA Grant UL1 RR024153 and NIH/NCRR/GCRC Grant M01 RR000056, and by a grant from the Paget's Foundation. The materials are the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System, Research and Development, and the VCU Transgenic/Knockout Mouse Core, supported in part by the Massey Cancer Center Support Grant P30 CA016059. J.P.B. reports having served as a consultant to Amgen, Sanofi-Aventis, Warner-Chilcott, Merck, E. Lily, Novartis, Servier. G.D.R. reports having served as a consultant to Amgen, Novartis, Celgene, and Millennium and received grant support from Novartis as well.

PY - 2011/1/5

Y1 - 2011/1/5

N2 - Paget's disease (PD) is characterized by abnormal osteoclasts (OCL) that secrete high IL-6 levels and induce exuberant bone formation. Because measles virus nucleocapsid gene (MVNP) and the p62P392L mutation are implicated in PD, marrows from 12 PD patients harboring p62P392L and eight normals were tested for MVNP expression and pagetic OCL formation. Eight out of twelve patients expressed MVNP and formed pagetic OCL in vitro, which were inhibited by antisense-MVNP. Four out of twelve patients lacked MVNP and formed normal OCL that were hyperresponsive to RANKL but unaffected by antisense-MVNP. Similarly, mice expressing only p62P394L formed normal OCL, while mice expressing MVNP in OCL, with or without p62 P394L, developed pagetic OCL and expressed high IL-6 levels dependent on p38MAPK activation. IL-6 deficiency in MVNP mice abrogated pagetic OCL development in vitro. Mice coexpressing MVNP and p62P394L developed dramatic Paget's-like bone lesions. These results suggest that p62 P394L and IL-6 induction by MVNP play key roles in PD.

AB - Paget's disease (PD) is characterized by abnormal osteoclasts (OCL) that secrete high IL-6 levels and induce exuberant bone formation. Because measles virus nucleocapsid gene (MVNP) and the p62P392L mutation are implicated in PD, marrows from 12 PD patients harboring p62P392L and eight normals were tested for MVNP expression and pagetic OCL formation. Eight out of twelve patients expressed MVNP and formed pagetic OCL in vitro, which were inhibited by antisense-MVNP. Four out of twelve patients lacked MVNP and formed normal OCL that were hyperresponsive to RANKL but unaffected by antisense-MVNP. Similarly, mice expressing only p62P394L formed normal OCL, while mice expressing MVNP in OCL, with or without p62 P394L, developed pagetic OCL and expressed high IL-6 levels dependent on p38MAPK activation. IL-6 deficiency in MVNP mice abrogated pagetic OCL development in vitro. Mice coexpressing MVNP and p62P394L developed dramatic Paget's-like bone lesions. These results suggest that p62 P394L and IL-6 induction by MVNP play key roles in PD.

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