scholarly journals Estrogen Receptor-Related Receptor α Impinges on the Estrogen Axis in Bone: Potential Function in Osteoporosis

Endocrinology ◽  
2002 ◽  
Vol 143 (9) ◽  
pp. 3658-3670 ◽  
Author(s):  
Edith Bonnelye ◽  
Vanessa Kung ◽  
Catherine Laplace ◽  
Deborah L. Galson ◽  
Jane E. Aubin
Keyword(s):  
Estrogen Receptor ◽  
Functional Role ◽  
Nuclear Factor Κb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Post Surgery ◽  
Rat Calvaria ◽  
Receptor Activator

Abstract The orphan nuclear estrogen receptor-related receptor α (ERRα) is expressed by osteoblastic cells and plays a functional role in osteoprogenitor proliferation and differentiation. To dissect further the role of ERRα in bone, we investigated the effects of estrogen (E2) on ERRα both in vitro and in vivo. Chronic treatment of fetal rat calvaria cells with E2-stimulated bone nodule formation and up-regulated ERRα mRNA expression at early (10 h and d 8) but not later times in culture, suggesting a link between ERRα and E2 during osteoprogenitor proliferation. ERRα mRNA levels were significantly lower in ovariectomized adult rat bones vs. those of sham-operated rats early (1 d and 1 wk) post surgery, but levels returned to control levels thereafter. ERRα is also expressed in osteoclasts (tartrate-resistant acid phosphatase + multinucleated cells) in vivo and in vitro (RAW 264.7 cells) and ovariectomization lowered the OPG/receptor activator of nuclear factor κB ligand expression ratio. Down-regulation of ERRα expression via antisense treatment of rat calvaria cells not only inhibited osteogenesis but also increased adipocyte colony formation and changed the OPG/receptor activator of nuclear factor κB ligand ratio. These data suggest that ERRα is regulated by estrogen in bone in which it may play a functional role at several levels (osteoblasts, adipocytes, and osteoclasts) in E2 deficiency diseases such as osteoporosis.

scholarly journals The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 398 ◽  
Author(s):  
Benjamin Navet ◽  
Kosei Ando ◽  
Jorge Vargas-Franco ◽  
Régis Brion ◽  
Jérome Amiaud ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Nuclear Factor Κb ◽  
Osteosarcoma Cell ◽  
Nuclear Factor ◽  
Osteosarcoma Cells ◽  
Cellular Processes ◽  
Receptor Activator ◽  
Rank Signaling

Background: Osteosarcoma is the most frequent form of malignant pediatric bone tumor. Despite the current therapeutic arsenal, patient life-expectancy remains low if metastases are detected at the time of diagnosis, justifying research into better knowledge at all stages of osteosarcoma ontogenesis and identification of new therapeutic targets. Receptor Activator of Nuclear factor κB (RANK)expression has been reported in osteosarcoma cells, raising the question of Receptor Activator of Nuclear factor κB Ligand (RANKL)/RANK signaling implications in these tumor cells (intrinsic), in addition to previously reported implications through osteoclast activation in the tumor microenvironment (extrinsic). Methods: Based on in vitro and in vivo experimentations using human and mouse osteosarcoma cell lines, the consequences on the main cellular processes of RANK expression in osteosarcoma cells were analyzed. Results: The results revealed that RANK expression had no impact on cell proliferation and tumor growth, but stimulated cellular differentiation and, in an immune-compromised environment, increased the number of lung metastases. The analysis of RANKL, RANK and osteoprotegerin (OPG) expressions in biopsies of a cohort of patients revealed that while RANK expression in osteosarcoma cells was not significantly different between patients with or without metastases at the time of diagnosis, the OPG/RANK ratio decreased significantly. Conclusion: Altogether, these results are in favor of RANKL-RANK signaling inhibition as an adjuvant for the treatment of osteosarcoma.

scholarly journals Periprosthetic Osteolysis: Mechanisms, Prevention and Treatment

2019 ◽  
Vol 8 (12) ◽  
pp. 2091 ◽  
Author(s):  
Stuart B. Goodman ◽  
Jiri Gallo
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Periprosthetic Osteolysis ◽  
Bone Implant ◽  
Joint Replacements ◽  
In Vivo Experiments ◽  
Mechanical Factors

Clinical studies, as well as in vitro and in vivo experiments have demonstrated that byproducts from joint replacements induce an inflammatory reaction that can result in periprosthetic osteolysis (PPOL) and aseptic loosening (AL). Particle-stimulated macrophages and other cells release cytokines, chemokines, and other pro-inflammatory substances that perpetuate chronic inflammation, induce osteoclastic bone resorption and suppress bone formation. Differentiation, maturation, activation, and survival of osteoclasts at the bone–implant interface are under the control of the receptor activator of nuclear factor kappa-Β ligand (RANKL)-dependent pathways, and the transcription factors like nuclear factor κB (NF-κB) and activator protein-1 (AP-1). Mechanical factors such as prosthetic micromotion and oscillations in fluid pressures also contribute to PPOL. The treatment for progressive PPOL is only surgical. In order to mitigate ongoing loss of host bone, a number of non-operative approaches have been proposed. However, except for the use of bisphosphonates in selected cases, none are evidence based. To date, the most successful and effective approach to preventing PPOL is usage of wear-resistant bearing couples in combination with advanced implant designs, reducing the load of metallic and polymer particles. These innovations have significantly decreased the revision rate due to AL and PPOL in the last decade.

In Vitro and in Vivo Nuclear Factor-κB Inhibitory Effects of the Cell-Penetrating Penetratin Peptide

2006 ◽  
Vol 69 (6) ◽  
pp. 2027-2036 ◽  
Author(s):  
Tamás Letoha ◽  
Erzsébet Kusz ◽  
Gábor Pápai ◽  
Annamária Szabolcs ◽  
József Kaszaki ◽  
...  
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Inhibitory Effects ◽  
Cell Penetrating

Fucoidans from Cucumaria frondosa ameliorates renal interstitial fibrosis via inhibition of PI3K/Akt/NF-κB signaling pathway

2022 ◽  
Author(s):  
Zhuo-yue Song ◽  
Mengru Zhu ◽  
Jun Wu ◽  
Tian Yu ◽  
Yao Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Interstitial Fibrosis ◽  
Protein Kinase B ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Renal Interstitial Fibrosis ◽  
Cucumaria Frondosa

The effects of Cucumaria frondosa polysaccharides (CFP) on renal interstitial fibrosis via regulating phosphatidylinositol-3-hydroxykinase/protein kinase-B/Nuclear factor-κB (PI3K/AKT/NF-κB) signaling pathway were investigated in vivo and in vitro in this research. A...

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