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MTOR TNFRSF11B (1 - 2 of 2)
PMID: 19393224
Down-regulation of mTOR leads to up-regulation of osteoprotegerin in bone marrow cells.
... of mTOR leads to ... of osteoprotegerin in ...   (details)

MTOR TNFRSF11B

Type:  negative regulation
Is this interaction correct?
Yes
No

Comments

PMID: 19393224

Down-regulation of mTOR leads to up-regulation of osteoprotegerin in bone marrow cells.
Source

Biochemical and biophysical research communications (6/19/2009)

Abstract

Down-regulation of mTOR leads to up-regulation of osteoprotegerin in bone marrow cells. Osteoprotegerin (OPG) /osteoclastogenesis inhibitory factor regulates bone mass by inhibiting osteoclastic bone resorption. mTOR, which is the mammalian target of rapamycin, is a kinase and central regulator of cell growth, proliferation, and survival. By using Rapamycin, we studied whether mTOR pathway is associated with OPG protein production in the mouse bone marrow-derived stromal cell line ST2. Rapamycin markedly increased the level of soluble OPG in ST2 cells. This antibiotic treatment resulted in the suppression of phosphorylation of mTOR. Rapamycin had no effects on the proliferation, differentiation, or apoptosis of the cells. Treatment with bone morphogenetic protein-4, which can induce OPG protein in ST2 cells, also resulted in a decrease in the density of the phospho-mTOR-band, suggesting that the suppression of the phospho-mTOR pathway is necessary for OPG production in ST2 cells. Thus, suitable suppression of mTOR phosphorylation is a necessary requirement for OPG production in bone marrow stromal cells.

PMID: 23331792
Rapamycin increases neuroblastoma xenograft and host stromal derived osteoprotegerin inhibiting osteolytic bone disease in a bone metastasis model.
... that Mammalian Target of Rapamycin (mTOR) inhibition upregulates OPG production ...   (details)

MTOR TNFRSF11B

Type:  negative regulation
Is this interaction correct?
Yes
No

Comments

PMID: 23331792

Rapamycin increases neuroblastoma xenograft and host stromal derived osteoprotegerin inhibiting osteolytic bone disease in a bone metastasis model.
Source

Journal of pediatric surgery (January 2013)

Abstract

Rapamycin increases neuroblastoma xenograft and host stromal derived osteoprotegerin inhibiting osteolytic bone disease in a bone metastasis model. [PURPOSE] Osteoprotegerin (OPG) is a decoy receptor for the Receptor of NF-?B (RANK) ligand that can inhibit osteoclastogenesis. Previous studies have suggested that Mammalian Target of Rapamycin (mTOR) inhibition upregulates OPG production. We tested the hypothesis that the mTOR inhibitor rapamycin could inhibit neuroblastoma bone metastases through its action on OPG. [EXPERIMENTAL DESIGN] An orthotopic model of bone metastasis was established. Mice with established disease were subsequently treated with rapamycin (5mg/kg IP daily) or vehicle control (DMSO 1: 1000). X-rays were obtained twice a week to detect pathologic fractures. Serum OPG levels were measured by ELISA after two weeks of treatment. [RESULTS] Mice with bone disease receiving rapamycin had increased serum levels of OPG in the CHLA-20 mice compared to controls (36.89pg/mL±3.90 vs 18.4pg/mL±1.67, p=0.004) and NB1691 tumor-bearing groups (46.03±2.67pg/mL vs 17.96±1.84pg/mL, p=0.001), and a significantly longer median time to pathologic fractures with CHLA-20 (103days vs 74.5days, p=0.014) and NB1691 xenografts. [CONCLUSION] In a xenograft model, increased OPG expression correlated with a delay to pathologic fracture suggesting a potential role for mTOR inhibitors in the treatment of neuroblastoma bone metastases.