Source:http://linkedlifedata.com/resource/pubmed/id/19762714
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2009-10-7
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| pubmed:abstractText |
Bone mass is maintained through the complementary activities of osteoblasts and osteoclasts; yet differentiation of either osteoblasts and osteoclasts engages the mitogen-activated protein kinase (MAPK) pathway. The MAPKs are negatively regulated by a family of dual-specificity phosphatases known as the MAPK phosphatases (MKPs). MKP-1 is a stress-responsive MKP that inactivates the MAPKs and plays a central role in macrophages; however, whether MKP-1 plays a role in the maintenance of bone mass has yet to be investigated. We show here, using a genetic approach, that mkp-1(-/-) female mice exhibited slightly reduced bone mass. We found that mkp-1(+/+) and mkp-1(-/-) mice had equivalent levels of bone loss after ovariectomy despite mkp-1(-/-) mice having fewer osteoclasts, suggesting that mkp-1(-/-) osteoclasts are hyperactive. Indeed, deletion of MKP1 led to a profound activation of osteoclasts in vivo in response to local lipopolysaccharide (LPS) injection. These results suggest a role for MKP-1 in osteoclasts, which originate from the fusion of macrophages. In support of these observations, receptor activator for nuclear factor-kappaB ligand induced the expression for MKP-1, and osteoclasts derived from mkp-1(-/-) mice had increased resorptive activity. Finally, receptor activator of nuclear factor-kappaB ligand-induced p38 MAPK and c-Jun NH2-terminal kinase activities were enhanced in osteoclasts derived from mkp-1(-/-) mice. Taken together, these results show that MKP-1 plays a role in the maintenance of bone mass and does so by negatively regulating MAPK-dependent osteoclast signaling.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Dual Specificity Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Dusp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogens,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/RANK Ligand
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1525-2191
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
175
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1564-73
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| pubmed:dateRevised |
2010-10-4
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| pubmed:meshHeading |
pubmed-meshheading:19762714-Animals,
pubmed-meshheading:19762714-Bone Density,
pubmed-meshheading:19762714-Bone Resorption,
pubmed-meshheading:19762714-Bone and Bones,
pubmed-meshheading:19762714-Cell Count,
pubmed-meshheading:19762714-Cell Differentiation,
pubmed-meshheading:19762714-Dual Specificity Phosphatase 1,
pubmed-meshheading:19762714-Enzyme Activation,
pubmed-meshheading:19762714-Estrogens,
pubmed-meshheading:19762714-Female,
pubmed-meshheading:19762714-Homeostasis,
pubmed-meshheading:19762714-Injections,
pubmed-meshheading:19762714-Lipopolysaccharides,
pubmed-meshheading:19762714-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:19762714-Male,
pubmed-meshheading:19762714-Mice,
pubmed-meshheading:19762714-Osteoblasts,
pubmed-meshheading:19762714-Osteoclasts,
pubmed-meshheading:19762714-Ovariectomy,
pubmed-meshheading:19762714-RANK Ligand
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| pubmed:year |
2009
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| pubmed:articleTitle |
Role of MKP-1 in osteoclasts and bone homeostasis.
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| pubmed:affiliation |
Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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