Corticosteroid receptors, macrophages and cardiovascular disease

Rickard, Amanda J.; Young, Morag J.

doi:10.1677/jme-08-0144

Cited by 85 publications

(53 citation statements)

References 122 publications

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“…Because this experiment included control rather than sham-operated animals, it is possible that cortisol released in response to the stress induced by surgery prevented a stronger osteoclast response in MKP1-deficient mice. 30 These results suggested, however, that MKP-1-deficient mice had osteoclasts that were hyperactive and hence were capable of resorbing equal quantities of bone compared with wild-type mice. We confirmed these results by inducing rapid formation and activation of osteoclasts in calvariae.…”

Section: Discussionmentioning

confidence: 97%

Role of MKP-1 in Osteoclasts and Bone Homeostasis

Carlson

Cui

Zhang

et al. 2009

The American Journal of Pathology

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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-B ligand induced the expression for MKP-1, and osteoclasts derived from mkp-1 ؊/؊ mice had increased resorptive activity. Finally, receptor activator of nuclear factor-B ligand-induced p38 MAPK and c-Jun NH 2 -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. Mitogen-activated protein kinases (MAPKs) constitute a family of serine/threonine protein kinases that transduce a wide array of extracellular signals into cellular responses, including cell growth, differentiation, and apoptosis. The three major subfamilies of MAPKs are extracellular signal-related kinases (ERKs), c-Jun NH 2 -terminal kinase (JNK), and p38 MAPK.1 MAPK activation occurs via phosphorylation on both threonine and tyrosine regulatory residues through the action of MAPK kinases, whereas dephosphorylation of either residue inactivates the MAPKs.2,3 MAPKs have been implicated in the control of bone mass, 4 which is maintained by both osteoblasts and osteoclasts.Osteoblasts are derived from mesenchymal stem cells and are responsible for the synthesis of the bone matrix and its subsequent calcification. 5,6 Although the physiological role of the MAPK pathway in osteoblasts had remained controversial, 7 recent work has established an important role for the ERK pathway in osteoblast differentiation that involves stimulation of RUNX2 phosphorylation and transcriptional activity.7 Osteoclasts are multinucleate cells derived from the hematopoietic monocyte/macrophage lineage and are responsible for the degradation of mineralized bone. Receptor activator of nuclear factor-B ligand (RANKL), which promotes differentiation and activation of osteoclasts, is expressed by osteoblasts, bone marrow stromal cells, and activated T-cells.8 -11 RANK...

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Section: Discussionmentioning

confidence: 97%

Role of MKP-1 in Osteoclasts and Bone Homeostasis

Carlson

Cui

Zhang

et al. 2009

The American Journal of Pathology

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“…As important tissue infl ammatory cells, macrophages undergo several stages of differentiation, including bone marrow hematopoietic stem cell, blood monocyte, and tissue macrophage ( 48 ). In diet-induced obesity, excess nutrition promotes more ATM recruitment and M1 polarization than in the normal diet state ( 3 ).…”

Section: Discussionmentioning

confidence: 99%

Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: a mechanism including AMPKα1/SIRT1

Dong¹,

Zhang²,

Zhang

et al. 2014

Journal of Lipid Research

243

167

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“…In addition, it was not determined which cells in the kidney were involved in the effects of IMD-1041, for the same reason. Previous reports on tissue injury by aldosterone have clearly shown that inflammation plays important roles in the remodeling of the heart, vasculature, and kidney [26,27]. Furthermore, emerging evidence suggests that aldosterone receptors are present in various types of cells, including endothelial cells, macrophages, vascular smooth cells, cardiac cells, and renal tubular and glomerular cells, and that activation of the aldosterone receptor on these cells could induce inflammation in the organs [26,27].…”

Section: Discussionmentioning

confidence: 99%