Localization of RANKL (receptor activator of NFκB ligand) mRNA and protein in skeletal and extraskeletal tissues

Kartsogiannis, Vicky; Zhou, Hong; Horwood, Nicole J.; Thomas, Russell J.; Hards, D.K.; Quinn, J; Niforas, Peter; Ng, KW; Martın, Thomas; Gillespie, Matthew T.

doi:10.1016/s8756-3282(99)00214-8

Cited by 305 publications

(244 citation statements)

References 38 publications

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“…In agreement with the previous study (32), the RANKL transcripts were found in bone, thymus, and spleen but not in intestine and kidney in WT and OPG Ϫ/Ϫ mice. Activated T cells released a large amount of RANKL.…”

Section: Discussionsupporting

confidence: 93%

“…First-strand cDNA was synthesized from total RNA with oligo(dT) [12][13][14][15][16][17][18] primer and Revertra Ace (Toyobo) and subjected to PCR amplification with Ex Taq polymerase (Takara). The specific primer pairs and temperature conditions were as follows: for mouse RANKL cDNA amplification, forward: 5Ј-CGCTC TGTTCCTGTACTTTCGAGCG-3Ј/reverse: 5Ј-TCGTGCTCCCTCCTTT CATCAGGTT-3; denaturation at 94°C for 2 min followed by 32 …”

Section: Rt-pcr Analysismentioning

confidence: 99%

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Osteoprotegerin Reduces the Serum Level of Receptor Activator of NF-κB Ligand Derived from Osteoblasts

Nakamichi

Udagawa

Kobayashi

et al. 2007

The Journal of Immunology

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Osteoprotegerin (OPG) is a decoy receptor for receptor activator of NF-κB ligand (RANKL). We previously reported that OPG deficiency elevated the circulating level of RANKL in mice. Using OPG−/− mice, we investigated whether OPG is involved in the shedding of RANKL by cells expressing RANKL. Osteoblasts and activated T cells in culture released a large amount of RANKL in the absence of OPG. OPG or a soluble form of receptor activator of NF-κB (the receptor of RANKL) suppressed the release of RANKL from those cells. OPG- and T cell-double-deficient mice showed an elevated serum RANKL level equivalent to that of OPG−/− mice, indicating that circulating RANKL is mainly derived from bone. The serum level of RANKL in OPG−/− mice was increased by ovariectomy or administration of 1α,25-dihydroxyvitamin D3. Expression of RANKL mRNA in bone, but not thymus or spleen, was increased in wild-type and OPG−/− mice by 1α,25-dihydroxyvitamin D3. These results suggest that OPG suppresses the shedding of RANKL from osteoblasts and that the serum RANKL in OPG−/− mice exactly reflects the state of bone resorption.

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Section: Discussionsupporting

confidence: 93%

Section: Rt-pcr Analysismentioning

confidence: 99%

Osteoprotegerin Reduces the Serum Level of Receptor Activator of NF-κB Ligand Derived from Osteoblasts

Nakamichi

Udagawa

Kobayashi

et al. 2007

The Journal of Immunology

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“…This osteoclastogenic cytokine is also expressed in synovial cells 22 and activated T cells 23 in synovial tissues in patients with RA, which causes a marked stimulation of osteoclastogenesis in these patients. Kartsogiannis et al 24 showed the expression of mRNA for RANKL in osteoclasts in normal bone by in situ hybridization. Roux et al 25 demonstrated the expression of RANKL in osteoclast-like multinucleated cells of human giant cell tumor using an immunohistochemical technique.…”

Section: Discussionmentioning

confidence: 99%

Possible involvement of MIP-1α in the recruitment of osteoclast progenitors to the distal tibia in rats with adjuvant-induced arthritis

Toh

Kukita

et al. 2004

Laboratory Investigation

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In the rat model of rheumatoid arthritis, a marked formation of osteoclasts is found in the distal tibia and the metatarsal bone. It was therefore postulated that osteoclast progenitors would be increased in the bone marrow cavities of rats with adjuvant-induced arthritis (AA rats). Bone marrow cells obtained from tibia of AA rats were cultured to form cells in the osteoclast lineage to access the number of osteoclast progenitors. Unexpectedly, only a suppressed level of osteoclast progenitors was detected in the diaphyseal bone marrow of tibia in AA rats. Distribution of osteoclast progenitors in the bone marrow cavity was examined, and it was shown that osteoclast progenitors accumulated in the distal tibia. Macrophage inflammatory protein (MIP)-1a, an osteoclastogenic CC chemokine, was expressed in ED-1-positive macrophages localizing in the distal tibia with marked bone destruction. Chemotaxis studies showed that MIP-1a expressed significant activity towards bone marrow cells. The suppressed level of osteoclastogenesis in bone marrow cells of AA rats was restored to a normal level by the addition of MIP-1a. It was suggested that MIP-1a is involved in the migration of osteoclast progenitors to the distal tibia as well as in osteoclastogenesis in AA rats. In these rats, in situ hybridization of the distal tibia with a high level of bone destruction showed significant expression of Receptor activator nuclear factor jB ligand (RANKL) messenger RNA in aggregates of multinucleated osteoclast-like cells present in the bone marrow cavity, a unique pathological feature for these rats. Migrated osteoclast progenitors are thought to be efficiently differentiated into osteoclasts in response to RANKL expressed by the aggregates of osteoclastlike cells under the influence of the MIP-1a. Such positive-feedback regulation of osteoclastogenesis could result in the highest recruitment of active osteoclasts in the area of marked bone destruction.

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“…Because RANKL mRNA was detected in osteoclasts (Kartsogiannis et al, 1999), RANKL is thought to be produced in osteoclasts rather than by osteoclastic incorporation of soluble RANKL proteins, which are secreted by osteoblasts/stromal cells in a paracrine manner. Our ultrastructural localization of RANKL in osteoclasts suggests that RANKL has regulatory function(s) associated with resorptive function at the ruffled border membranes.…”

Section: Discussionmentioning

confidence: 99%

“…Ultrathin sections mounted on Formvar-coated nickel grids were first treated with 10% bovine serum albumin (BSA) in 0.01 M phosphate-buffered saline (PBS) for 1 hr to block nonspecific binding of antibody. The sections were then incubated with rabbit antiserum raised against either RANKL (donated by Dr. M. Gillespie, St. Vincent's Institute of Medical Research, Victoria, Australia) (Kartsogiannis et al, 1999) diluted 1:100 with 1% BSA/PBS or vacuolar-type H ϩ -ATPase (donated by Dr. Moriyama, Hiroshima University, Hiroshima, Japan) diluted 1:500 with 1% BSA/ PBS, overnight at 4°C. After incubation, the sections were rinsed with PBS and incubated with goat anti-rabbit IgG, conjugated with 10 nm colloidal gold particles (BioCell Research Laboratories, Cardiff, UK) diluted 1:100 with PBS for 1 hr at room temperature.…”

Section: Histological Cytochemical and Immunohistochemical Examinatmentioning

confidence: 99%

Osteoclast induction in periodontal tissue during experimental movement of incisors in osteoprotegerin‐deficient mice

et al. 2002

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Osteoprotegerin (OPG) is a novel secreted member of the tumor necrosis factor (TNF) receptor superfamily that negatively regulates osteoclastogenesis. The receptor activator of the NFKB ligand (RANKL) is one of the key regulatory molecules in osteoclast formation and binds to OPG. In this study, it was suggested that OPG and RANKL are involved in alveolar bone remodeling during orthodontic tooth movement. We examined RANKL localization and osteoclast induction in periodontal tissues during experimental movement of incisors in OPG-deficient mice. To produce orthodontic force, an elastic band was inserted between the upper right and left incisors for 2 or 5 days, and the dissected maxillae were examined for cytochemical and immunocytochemical localization of tartrate-resistant acid phosphatase (TRAP), vacuolar-type H ϩ -ATPase, and RANKL. Compared to wild-type OPG (ϩ/ϩ) littermates, TRAP-positive multinucleated cells were markedly induced in the periodontal ligament (PDL) on the compressed side and in the adjacent alveolar bone of OPG-deficient mice. These multinucleated cells exhibited intense vacuolar-type H ϩ -ATPase along the ruffled border membranes. Because of accelerated osteoclastic resorption in OPG-deficient mice, alveolar bone was severely destroyed and partially perforated at 2 and 5 days after force application. In both wild-type and OPG-deficient mice, RANKL expression became stronger at 2 and 5 days after force application than before force application. There was no apparent difference in intensity of RANKL expression between OPG (ϩ/ϩ) littermates and OPGdeficient mice. In both wild-type and OPG-deficient mice, expression of RANKL protein was detected in osteoblasts, fibroblasts, and osteoclasts mostly located in resorption lacunae. These results suggest that during orthodontic tooth movement, RANKL and OPG in the periodontal tissues are important determinants regulating balanced alveolar bone resorption. Anat Rec 266:218 -225, 2002.

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Localization of RANKL (receptor activator of NFκB ligand) mRNA and protein in skeletal and extraskeletal tissues

Cited by 305 publications

References 38 publications

Osteoprotegerin Reduces the Serum Level of Receptor Activator of NF-κB Ligand Derived from Osteoblasts

Osteoprotegerin Reduces the Serum Level of Receptor Activator of NF-κB Ligand Derived from Osteoblasts

Possible involvement of MIP-1α in the recruitment of osteoclast progenitors to the distal tibia in rats with adjuvant-induced arthritis

Osteoclast induction in periodontal tissue during experimental movement of incisors in osteoprotegerin‐deficient mice

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