Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand

Hsu, Hailing; Lacey, David L.; Dunstan, Colin R.; Solovyev, Irina; Colombero, Anne; Timms, Emma; Tan, Helming; Elliott, Gary; Kelley, Michael J.; Sarosi, Ildiko; Wang, Ling; Xia, Xing-Zhong; Elliott, Robin; Chiu, Laura; Black, Tabitha; Scully, Sheila; Capparelli, Casey; Morony, Sean; Shimamoto, Grant; Bass, Michael; Boyle, William J.

doi:10.1073/pnas.96.7.3540

Cited by 1,491 publications

(1,163 citation statements)

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“…RANK mRNA is expressed in many tissues, including skeletal muscle, liver, small intestine and colon, thymus, and adrenal gland (9), yet expression of RANK protein appears to be restricted to osteoclasts and osteoclast precursor cells, T cells, dendritic cells, and endothelial cells (9)(10)(11)32). This study is the first to show that freshly isolated CD14ϩ PBMCs express not only RANK mRNA but also RANK immunoreactivity on their surface, as shown by FACS analysis.…”

Section: Discussionmentioning

confidence: 71%

“…RANKL mediates osteoclastogenesis as well as osteoclast activation and survival in vivo via its receptor RANK (10,11). RANK mRNA is expressed in many tissues, including skeletal muscle, liver, small intestine and colon, thymus, and adrenal gland (9), yet expression of RANK protein appears to be restricted to osteoclasts and osteoclast precursor cells, T cells, dendritic cells, and endothelial cells (9)(10)(11)32).…”

Section: Discussionmentioning

confidence: 99%

“…RANK, which is expressed on osteoclasts and osteoclast precursor cells, T cells, and dendritic cells (9)(10)(11), mediates intracellular signals obligatory for osteoclastogenesis as well as osteoclast activation and survival in vivo (11,12). The effects are mediated through RANKL, a member of the tumor necrosis factor superfamily that is expressed on osteoblast/stromal cells and activated T cells (13,14).…”

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confidence: 99%

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Expression and function of RANK in human monocyte chemotaxis

Mosheimer

Kaneider

Feistritzer

et al. 2004

Arthritis & Rheumatism

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Objective. RANKL, a member of the tumor necrosis factor superfamily, is a central regulator of osteoclast recruitment and activation. Whether RANKL affects monocyte locomotion in vitro via RANK and a possible signaling pathway were investigated.Methods. Monocytes were obtained from venous blood of healthy donors. Cell migration was studied by micropore filter assays. The signaling mechanisms required for RANKL-dependent migration were tested using signaling enzyme blockers and Western blot analyses. Expression of RANK messenger RNA (mRNA) in monocytes was demonstrated by reverse transcriptasepolymerase chain reaction, and receptor expression on cell surface was investigated by fluorescence-activated cell sorting analyses.Results. RANKL significantly stimulated monocyte chemotaxis via activation of phosphatidylinositol 3-kinase, phosphodiesterase, and Src kinase. The effect on migration was inhibited by osteoprotegerin, which is the decoy receptor for RANKL. Expression of RANK receptor mRNA was shown, and synthesis of RANK in monocytes was suggested by the detection of RANK immunoreactivity on the cell surface.Conclusion. These data suggest that RANK is expressed by monocytes whose activation by RANKL stimulates directed migration involving phosphatidylinositol 3-kinase, phosphodiesterase, and Src kinases.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Expression and function of RANK in human monocyte chemotaxis

Mosheimer

Kaneider

Feistritzer

et al. 2004

Arthritis & Rheumatism

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“…RANK, a heterotrimer containing 3 molecular intracellular domains (I, II, and III), belongs to the TNF receptor superfamily. It is expressed on the surface of hematopoietic osteoclast progenitors, mature osteoclasts, chondrocytes, mammary gland epithelial cells, trophoblast cells, dendritic cells (DCs), mature T cells, and hematopoietic precursors (4,20). Binding of RANK with its ligand RANKL results in osteoclastogenesis of monocyte/macrophage progenitor cells to osteoclasts and activation of mature osteoclasts (7,20).…”

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confidence: 99%

The RANK/RANKL/osteoprotegerin system in rheumatoid arthritis: New insights from animal models

Neumann

Müller‐Ladner

2005

Arthritis & Rheumatism

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“…Recruitment and maturation of osteoclasts for bone resorption require two important molecules, colony-stimulating factor (Felix et al, 1990;Cecchini et al, 1997) and receptor activator of NF-jB ligand (RANKL) (Hsu et al, 1999;Wada et al, 2006), both of which are expressed by osteoblasts. The binding of RANKL to the RANK receptor on osteoclasts activates osteoclast differentiation and bone resorption.…”

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confidence: 99%

Molecular Variations Related to the Regional Differences in Periosteal Growth at the Mandibular Ramus

Sun

Tee

2010

The Anatomical Record

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Periosteal growth at human mandibular ramus is characterized by bone apposition at the posterior border and resorption at the anterior border. Molecular control of this regional variation is unclear. This study examined the expression of several molecules involved in bone apposition/ resorption at these regions in vivo and in vitro. By using growing pigs as a model, the periosteal growth was assessed at the mandibular ramus by vital staining and histological observations. In parallel, periosteal tissues were harvested and pulverized for RNA and protein extraction. Periosteal cells were also isolated, expanded in osteogenic media, and subjected to a single dose of dynamic tensile strain (0, 5, or 10% magnitude at 0.5 Hz) to examine their responses to mechanical loading. Real-time RT-PCR and Western blot analyses were used to examine mRNA and protein expression from periosteal tissues and cultured cells. Histological observation confirmed an anterior-resorption/posterior-apposition pattern in the pig mandibular ramus. Both in vivo tissue and in vitro cells demonstrated greater mRNA expression of receptor activator of NF-jB ligand (RANKL)/osteoprotegerin (OPG) ratio and bone morphogenetic protein 2 (BMP2) at the anterior region, while OPG expression at the anterior region was lower than the posterior region. In response to the application of a single dose of dynamic tensile strain, cultured periosteal cells appeared to change the expression profile of osteogenic markers but not that of RANKL/OPG and BMP2. These findings suggest that the unique regional variation of periosteal activity at the mandibular ramus is regulated by a differential expression of RANKL/OPG ratio (likely through differential induction of OPG) and BMP2. Anat Rec, 294:79-87, 2011. V V C 2010 Wiley-Liss, Inc.Key words: periosteum; mandibular growth; RANKL/OPG; tissue engineering; cell loadingHuman mandibular growth is mainly through endochondral bone formation at the condyles and intramembranous bone formation at the periosteum (Enlow and Hans, 1996). While condylar growth provides the overall elongation and rotation of the mandible (Bjork and Skieller, 1983), periosteal activity causes extensive surface modeling/remodeling or reshaping of the mandible (Enlow and Hans, 1996). One striking feature of mandibular periosteal activity is at the ramus, where bone resorption takes place at the anterior (rostral) border whereas bone apposition at the posterior (caudal) border (Robinson and Sarnat, 1955;Seiton and Engel, 1969;Hans et al., 1995). At the cell level, osteogenic proliferation is concentrated at the appositional posterior ramal region, whereas osteoclasts are mainly present at the resorptive anterior region (Ochareon and Herring, 2007). However, the molecular mechanisms related to these differential periosteal activities are mostly unknown.

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Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand

Cited by 1,491 publications

References 26 publications

Expression and function of RANK in human monocyte chemotaxis

Expression and function of RANK in human monocyte chemotaxis

The RANK/RANKL/osteoprotegerin system in rheumatoid arthritis: New insights from animal models

Molecular Variations Related to the Regional Differences in Periosteal Growth at the Mandibular Ramus

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