Expression and function of RANK in human monocyte chemotaxis

Mosheimer, Birgit A.; Kaneider, Nicole C.; Feistritzer, Clemes; Sturn, Daniel H.; Wiedermann, Christian J.

doi:10.1002/art.20352

Cited by 45 publications

(32 citation statements)

References 39 publications

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“…RANKL has a chemo-attractant effect on peripheral blood monocytes (15,16). Therefore, local release of RANKL by chondrocytes and induction of its expression by BMP2 could mediate this OCP egression.…”

Section: Normal Bone Modelingmentioning

confidence: 99%

Functions of RANKL/RANK/OPG in bone modeling and remodeling

Boyce

Xing

2008

Archives of Biochemistry and Biophysics

1,438

1,058

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The discovery of the RANKL/RANK/OPG system in the mid 1990s for the regulation of bone resorption has led to major advances in our understanding of how bone modeling and remodeling are regulated. It had been known for many years before this discovery that osteoblastic stromal cells regulated osteoclast formation, but it had not been anticipated that they would do this through expression of members of the TNF superfamily: receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), or that these cytokines and signaling through receptor activator of NF-κB (RANK) would have extensive functions beyond regulation of bone remodeling. RANKL/RANK signaling regulates osteoclast formation, activation and survival in normal bone modeling and remodeling and in a variety of pathologic conditions characterized by increased bone turnover. OPG protects bone from excessive resorption by binding to RANKL and preventing it from binding to RANK. Thus, the relative concentration of RANKL and OPG in bone is a major determinant of bone mass and strength. Here, we review our current understanding of the role of the RANKL/RANK/ OPG system in bone modeling and remodeling. KeywordsBone resorption; osteoclasts; RANKL; RANK; OPG Normal bone modelingWith the exception of the bones of the calvaria, all bones in the mammalian skeleton are preformed in cartilage moulds from mesenchymal progenitors, which under appropriate stimuli also have the potential to differentiate into a variety of tissue types, including fibrous tissue, fat and muscle. Chondrocytes proliferate near the ends of the cartilage moulds to drive their longitudinal growth, while others in the centers of undergo hypertrophic differentiation. The hypertrophic chondrocytes at the periphery of the centers of these moulds are invaded by blood vessels and undergo apoptosis. Some of this hypertrophic cartilage survives as thin islands of cartilage in the centers of ossification in growing bones. Osteoblasts, which differentiate from progenitors in a collar of connective tissue around the middle of the bones where vascular invasion takes place, follow the endothelial cells and lay down bone matrix on the surfaces of these islands of cartilage to form bone struts or trabeculae (1). Osteoclast precursors (OCPs), derived from progenitors in the spleen and liver are attracted from blood in the invading blood vessels close to newly formed bone trabeculae. These osteoclast precursors fuse with one

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Section: Normal Bone Modelingmentioning

confidence: 99%

Functions of RANKL/RANK/OPG in bone modeling and remodeling

Boyce

Xing

2008

Archives of Biochemistry and Biophysics

1,438

1,058

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“…Migration of cells into nitrocellulose to gradients of recombinant visfatin was measured under use of a 48-well Boyden microchemotaxis chamber (Neuroprobe) in which an upper chamber is separated from a lower chamber by a 5-m pore-size filter (Sartorius) (26).…”

Section: Chemotaxismentioning

confidence: 99%

Visfatin, an Adipocytokine with Proinflammatory and Immunomodulating Properties

Moschen

Kaser

Enrich

et al. 2007

The Journal of Immunology

820

735

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Adipocytokines are mainly adipocyte-derived cytokines regulating metabolism and as such are key regulators of insulin resistance. Some adipocytokines such as adiponectin and leptin affect immune and inflammatory functions. Visfatin (pre-B cell colony-enhancing factor) has recently been identified as a new adipocytokine affecting insulin resistance by binding to the insulin receptor. In this study, we show that recombinant visfatin activates human leukocytes and induces cytokine production. In CD14+ monocytes, visfatin induces the production of IL-1β, TNF-α, and especially IL-6. Moreover, it increases the surface expression of costimulatory molecules CD54, CD40, and CD80. Visfatin-stimulated monocytes show augmented FITC-dextran uptake and an enhanced capacity to induce alloproliferative responses in human lymphocytes. Visfatin-induced effects involve p38 as well as MEK1 pathways as determined by inhibition with MAPK inhibitors and we observed activation of NF-κB. In vivo, visfatin induces circulating IL-6 in BALB/c mice. In patients with inflammatory bowel disease, plasma levels of visfatin are elevated and its mRNA expression is significantly increased in colonic tissue of Crohn’s and ulcerative colitis patients compared with healthy controls. Macrophages, dendritic cells, and colonic epithelial cells might be additional sources of visfatin as determined by confocal microscopy. Visfatin can be considered a new proinflammatory adipocytokine.

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“…28,37 Perhaps RANKL (and OPG) production by OB-like cells regulates OC formation and activity in atherogenic lesions. Furthermore, because RANKL can stimulate chemokine release, matrix metalloproteinase (MMP)-9 activity, and monocyte/macrophage matrix migration, [47][48][49][50] it might contribute to these crucial processes during cell recruitment and infiltration into atherogenic lesions. Like atherosclerosis, calcific aorta valve stenosis involves pronounced inflammation with activated macrophages and T cells, initiation of an active bone developmental program, and increased RANKL staining along with fewer OPG-expressing cells in focal calcification areas.…”

Section: Rankl Rank and Opg Expression In Normal And Pathological Vmentioning

confidence: 99%

“…Because RANKL also stimulates the recruitment, survival, and bone-resorptive activity of OCs, 9 -13,15,47,49,50 inflammatory-activated ECs expressing RANKL are poised to contribute to the in vivo appearance, function, and longevity of OC-like cells, which arise in advanced calcified atherosclerotic lesions and participate in remodeling bone formed in the vessel wall. 22,27,39,46,88 EC-associated RANKL might also enhance the recruitment and infiltration of monocyte/macrophages [47][48][49][50] that stimulate VSMC mineralization in atherosclerosis 1,20,44,52,88 and trigger monocyte production of MMP-9 47 that supports cell infiltration and atherosclerotic plaque growth.…”

Section: Rankl/rank and Vascular Cellsmentioning

confidence: 99%

Regulation of Vascular Calcification by Osteoclast Regulatory Factors RANKL and Osteoprotegerin

Collin‐Osdoby

2004

Circulation Research

409

207

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Abstract-Vascular calcification often occurs with advancing age, atherosclerosis, various metabolic disorders such as diabetes mellitus and end-stage renal disease, or in rare genetic diseases, leading to serious clinical consequences. Such mineralization can occur at various sites (cardiac valves, arterial intima or media, capillaries), involve localized or diffuse widespread calcification, and result from numerous causes that provoke active inflammatory and osteogenic processes or disordered mineral homeostasis. Although valuable research has defined many key factors and cell types involved, surprising new insights continue to arise that deepen our understanding and suggest novel research directions or strategies for clinical intervention in calcific vasculopathies. One emerging area in vascular biology involves the RANKL/RANK/OPG system, molecules of the tumor necrosis factor-related family recently discovered to be critical regulators of immune and skeletal biology. Evidence is accumulating that such signals may be expressed, regulated, and function in vascular physiology and pathology in unique ways to promote endothelial cell survival, angiogenesis, monocyte or endothelial cell recruitment, and smooth muscle cell osteogenesis and calcification. Concerted research efforts are greatly needed to understand these potential roles, clarify whether RANKL (receptor activator of nuclear factor B ligand) promotes and osteoprotegerin (OPG) protects against vascular calcification, define how OPG genetic polymorphisms relate to cardiovascular disease, and learn whether elevated serum OPG levels reflect endothelial dysfunction in patients. Overall, the RANKL/RANK/OPG system may mediate important and complex links between the vascular, skeletal, and immune systems. Thus, these molecules may play a central role in regulating the development of vascular calcification coincident with declines in skeletal mineralization with age, osteoporosis, or disease.

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Expression and function of RANK in human monocyte chemotaxis

Cited by 45 publications

References 39 publications

Functions of RANKL/RANK/OPG in bone modeling and remodeling

Functions of RANKL/RANK/OPG in bone modeling and remodeling

Visfatin, an Adipocytokine with Proinflammatory and Immunomodulating Properties

Regulation of Vascular Calcification by Osteoclast Regulatory Factors RANKL and Osteoprotegerin

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