Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency.

Ammann, Patrick; Rizzoli, René; Bonjour, J. P.; Bourrin, S.; Meyer, Jean‐Marc; Vassalli, Pierre; García, Irene

doi:10.1172/jci119333

Cited by 298 publications

(145 citation statements)

References 36 publications

(36 reference statements)

Supporting

Mentioning

138

Contrasting

Unclassified

Order By: Relevance

“…BMSCs were seeded at a density of 5,000 cells per cm 2 and routinely cultured in a growth medium consisting of DMEM containing 10% FCS, 1% penicillin-streptomycin, and 1% L-glutamine. Cells were maintained at 37°C in a humidified atmosphere with 5% CO 2 in air for 1 or 7 days.…”

Section: Cell Culturementioning

confidence: 99%

“…Interfering with TNF-α and IL-1β action may also be beneficial in preventing bone loss in diseases not usually considered as inflammatory, such as post-menopausal osteoporosis. Indeed, ovariectomized mice do not lose bone in absence of TNF-α [2,3] or IL-1 [3][4][5]. Moreover, bone resorption due to estrogen deficiency in women can be blocked by etanercept and anakinra, which are inhibitors of TNF-α or IL-1β respectively [6].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

et al. 2011

View full text Add to dashboard Cite

1 IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodelingsuggested that expression of IL-33, in contrast to that of IL-1β, is not repressed by PPARγ, likely explaining why IL-33, but not IL-1β, is expressed in adipocytes. The IL-33 receptor ST2L is not constitutively expressed in human bone marrow stromal cells, osteoblasts or CD14-positive monocytes, and IL-33 has no effect on these cells. In addition, although ST2L mRNA is induced by TNF-α and IL-1β in bone marrow stromal cells, IL-33 has the same effects as TNF-α and IL-1β, and, therefore, the biological activity of IL-33 may be redundant in this system. In agreement with this hypothesis, MC3T3-E1 osteoblast-like cells constitutively express ST2L mRNA, and in these cells IL-33 and TNF-α/IL-1β similarly decrease osteocalcin RNA levels in these cells. In conclusion, our results suggest that IL-33 has no direct effects on normal bone remodeling.

show abstract

Section: Cell Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The compensatory increase in bone formation that follows ovx is mitigated by some of these factors, primarily TNF and IL-7, which blunt osteoblastogenesis (15,16). The pathogenic role of cytokines distinct from RANKL and OPG has been established by studies demonstrating that the silencing of TNF, IL-1, IL-6, IL-7, and M-CSF prevents ovx-induced bone loss (17)(18)(19)(20)(21)(22)(23).…”

mentioning

confidence: 99%

Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand

Li¹,

Tawfeek²,

Bedi³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

162

149

View full text Add to dashboard Cite

The bone loss induced by ovariectomy (ovx) has been linked to increased production of osteoclastogenic cytokines by bone marrow cells, including T cells and stromal cells (SCs). It is presently unknown whether regulatory interactions between these lineages contribute to the effects of ovx in bone, however. Here, we show that the T-cell costimulatory molecule CD40 ligand (CD40L) is required for ovx to expand SCs; promote osteoblast proliferation and differentiation; regulate the SC production of the osteoclastogenic factors macrophage colony-stimulating factor, receptor activator of nuclear factor-κB ligand, and osteoprotegerin; and upregulate osteoclast formation. CD40L is also required for ovx to activate T cells and stimulate their production of TNF. Accordingly, ovx fails to promote bone loss and increase bone resorption in mice depleted of T cells or lacking CD40L. Therefore, cross-talk between T cells and SCs mediated by CD40L plays a pivotal role in the disregulation of osteoblastogenesis and osteoclastogenesis induced by ovx.estrogen | osteoporosis M enopause results in decreased production of estrogen (E) and a parallel increase in FSH levels, which together stimulate bone resorption (1) and cause a period of rapid bone loss that is central for the onset of postmenopausal osteoporosis (2). The acute effects of menopause are modeled by ovariectomy (ovx) which, like natural menopause, stimulates bone resorption by increasing osteoclast (OC) formation (3, 4) and lifespan (5, 6). The net bone loss caused by ovx is limited by an increase in bone formation resulting from stimulated osteoblast (OB) formation (7). This compensation is fueled by an expansion of the pool of bone marrow (BM) stromal cells (SCs), increased commitment of SCs to the osteoblastic lineage (7), and enhanced proliferation of early OB precursors (8). The stimulatory effect of ovx on SCs is equally relevant for osteoclastogenesis because one of the consequences of E deprivation is the formation of osteoblastic cells with increased osteoclastogenic activity (9), that is, the capacity to support OC formation.OC formation occurs when bone marrow macrophages (BMMs) are stimulated by the osteoclastogenic factors receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) (10, 11); however, in conditions of E deficiency, the secretion of the RANKL decoy receptor osteoprotegerin (OPG) decreased (12

show abstract

“…TNF-α, a pro-inflammatory cytokine, has been implicated in the early events related to osteoblast cell destruction. Suppression of TNF-α production or blockade of its interaction with its cellular receptors significantly inhibits deleterious effects in related osteoporotic diseases [24][25][26][27] . TNF-α activates several intracellular signaling pathways, including the AP-1 pathway, the MAPK pathway, and the JNK pathway in osteoblastic cells [28][29][30] .…”

Section: Discussionmentioning

confidence: 99%

Sirt1 overexpression protects murine osteoblasts against TNF-α-induced injury in vitro by suppressing the NF-κB signaling pathway

et al. 2012

View full text Add to dashboard Cite

Aim: Sirtuin 1 (Sirt1) is the class III histone/protein deacetylase that interferes with the NF-κB signaling pathway, thereby has antiinflammatory function. This study was undertaken to investigate whether Sirt1 could protect osteoblasts against TNF-α-induced injury in vitro. Methods: Murine osteoblastic cell line, MC3T3-E1, was used. Overexpress of Sirt1 protein in MC3T3-E1 cells was made by transfection the cells with Sirt1-overexpressing adenovirus. The levels of mRNAs and proteins were determined with qRT-PCR and Western blotting, respectively. The activity of NF-κB was examined using NF-κB luciferase assay. The NO concentration was measured using the Griess method. Results: Treatment of MC3T3-E1 cells with TNF-α (2.5-10 ng/mL) suppressed Sirt1 protein expression in a concentration-dependent manner. TNF-α (5 ng/mL) resulted in an increase in apoptosis and a reduction in ALP activity in the cells. Overexpression of Sirt1 in the cells significantly attenuated TNF-α-induced injury through suppressing apoptosis, increasing ALP activity, and increasing the expression of Runx2 and osteocalcin mRNAs. Furthermore, overexpression of Sirt1 in the cells significantly suppressed TNF-α-induced NF-κB activation, followed by reducing the expression of iNOS and NO formation. Sirt1 activator resveratrol (10 µmol/L) mimicked the protection of the cells by Sirt1 overexpression against TNF-α-induced injury, which was reversed by the Sirt1 inhibitor EX-527 (5 µmol/L). Conclusion: Overexpression of Sirt1 protects MC3T3-E1 osteoblasts aganst TNF-α-induced cell injury in vitro, at least in part, via suppressing NF-κB signaling. Sirt1 may be a novel therapeutic target for treating rheumatoid arthritis-related bone loss.

show abstract

Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency.

Cited by 298 publications

References 36 publications

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

IL-33 is expressed in human osteoblasts, but has no direct effect on bone remodeling

Ovariectomy disregulates osteoblast and osteoclast formation through the T-cell receptor CD40 ligand

Sirt1 overexpression protects murine osteoblasts against TNF-α-induced injury in vitro by suppressing the NF-κB signaling pathway

Contact Info

Product

Resources

About