Role of Phytochemicals in the Prevention of Menopausal Bone Loss: Evidence from In Vitro and In Vivo, Human Interventional and Pharmacokinetic Studies

2009 ◽  
Vol 16 (9) ◽  
pp. 1138-1157 ◽  
Author(s):  
Kunal Sharan ◽  
Jawed Siddiqui ◽  
Gaurav Swarnkar ◽  
Rakesh Maurya ◽  
Naibedya Chattopadhyay
Keyword(s):  
Bone Loss ◽  
Pharmacokinetic Studies

scholarly journals The Role of IL-1βin the Bone Loss during Rheumatic Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Piero Ruscitti ◽  
Paola Cipriani ◽  
Francesco Carubbi ◽  
Vasiliki Liakouli ◽  
Francesca Zazzeroni ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Rheumatic Diseases ◽  
Nuclear Factor Kappa B ◽  
Inflammatory Diseases ◽  
Receptor Activator ◽  
Main Factor

Several inflammatory diseases have been associated with increased bone resorption and fracture rates and different studies supported the relation between inflammatory cytokines and osteoclast activity. The main factor required for osteoclast activation is the stimulation by receptor activator of nuclear factor kappa-B ligand (RANKL) expressed on osteoblasts. In this context, interleukin- (IL-) 1β, one of the most powerful proinflammatory cytokines, is a strong stimulator of in vitro and in vivo bone resorption via upregulation of RANKL that stimulates the osteoclastogenesis. The resulting effects lead to an imbalance in bone metabolism favouring bone resorption and osteoporosis. In this paper, we review the available literature on the role of IL-1βin the pathogenesis of bone loss. Furthermore, we analysed the role of IL-1βin bone resorption during rheumatic diseases and, when available, we reported the efficacy of anti-IL-1βtherapy in this field.

scholarly journals The Non-Erythropoietic EPO Analogue Cibinetide Inhibits Osteoclastogenesis In Vitro and Increases Bone Mineral Density in Mice

2021 ◽  
Vol 23 (1) ◽  
pp. 55
Author(s):  
Zamzam Awida ◽  
Almog Bachar ◽  
Hussam Saed ◽  
Anton Gorodov ◽  
Nathalie Ben-Califa ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Loss ◽  
Bone Mineral ◽  
Molecular Mechanisms ◽  
Mineral Density ◽  
Female Mice ◽  
Epo Receptor

The two erythropoietin (EPO) receptor forms mediate different cellular responses to erythropoietin. While hematopoiesis is mediated via the homodimeric EPO receptor (EPOR), tissue protection is conferred via a heteromer composed of EPOR and CD131. In the skeletal system, EPO stimulates osteoclast precursors and induces bone loss. However, the underlying molecular mechanisms are still elusive. Here, we evaluated the role of the heteromeric complex in bone metabolism in vivo and in vitro by using Cibinetide (CIB), a non-erythropoietic EPO analogue that exclusively binds the heteromeric receptor. CIB is administered either alone or in combination with EPO. One month of CIB treatment significantly increased the cortical (~5.8%) and trabecular (~5.2%) bone mineral density in C57BL/6J WT female mice. Similarly, administration of CIB for five consecutive days to female mice that concurrently received EPO on days one and four, reduced the number of osteoclast progenitors, defined by flow cytometry as Lin−CD11b−Ly6Chi CD115+, by 42.8% compared to treatment with EPO alone. In addition, CIB alone or in combination with EPO inhibited osteoclastogenesis in vitro. Our findings introduce CIB either as a stand-alone treatment, or in combination with EPO, as an appealing candidate for the treatment of the bone loss that accompanies EPO treatment.

scholarly journals Anti–IL-20 monoclonal antibody inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss

2011 ◽  
Vol 208 (9) ◽  
pp. 1849-1861 ◽  
Author(s):  
Yu-Hsiang Hsu ◽  
Wei-Yu Chen ◽  
Chien-Hui Chan ◽  
Chih-Hsing Wu ◽  
Zih-Jie Sun ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Loss ◽  
Therapeutic Potential ◽  
Osteoclast Differentiation ◽  
Bone Destruction ◽  
Osteoporotic Bone ◽  
Mineral Density

IL-20 is a proinflammatory cytokine of the IL-10 family that is involved in psoriasis, rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about the role of IL-20 in bone destruction. We explored the function of IL-20 in osteoclastogenesis and the therapeutic potential of anti–IL-20 monoclonal antibody 7E for treating osteoporosis. Higher serum IL-20 levels were detected in patients with osteopenia and osteoporosis and in ovariectomized (OVX) mice. IL-20 mediates osteoclastogenesis by up-regulating the receptor activator of NF-κB (RANK) expression in osteoclast precursor cells and RANK ligand (RANKL) in osteoblasts. 7E treatment completely inhibited osteoclast differentiation induced by macrophage colony-stimulating factor (M-CSF) and RANKL in vitro and protected mice from OVX-induced bone loss in vivo. Furthermore, IL-20R1–deficient mice had significantly higher bone mineral density (BMD) than did wild-type controls. IL-20R1 deficiency also abolished IL-20–induced osteoclastogenesis and increased BMD in OVX mice. We have identified a pivotal role of IL-20 in osteoclast differentiation, and we conclude that anti–IL-20 monoclonal antibody is a potential therapeutic for protecting against osteoporotic bone loss.

scholarly journals Disruption of claudin-18 diminishes ovariectomy-induced bone loss in mice

2013 ◽  
Vol 304 (5) ◽  
pp. E531-E537 ◽  
Author(s):  
Ha-Young Kim ◽  
Catrina Alarcon ◽  
Sheila Pourteymour ◽  
Jon E. Wergedal ◽  
Subburaman Mohan
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Negative Regulator ◽  
Skeletal Phenotype ◽  
Estrogen Effects ◽  
Total Body ◽  
Deficient Mice

Claudin-18 (Cldn-18), a member of the tight junction family of proteins, is a negative regulator of RANKL-induced osteoclast differentiation and bone resorption (BR) in vivo. Since estrogen deficiency decreases bone mass in part by a RANKL-mediated increase in BR, we evaluated whether estrogen regulates Cldn-18 expression in bone. We found that Cldn-18 expression was reduced in the bones of estrogen deficient mice, whereas it was increased by estrogen treatment in osteoblasts and osteoclasts in vitro. We next evaluated the role of Cldn-18 in mediating estrogen-induced bone loss. Cldn-18 knockout (KO) and littermate wild-type (WT) mice were ovariectomized (OVX) or sham operated at 6 wk of age, and the skeletal phenotype was evaluated at 14 wk of age. PIXImus revealed that total body, femur, and lumbar BMD were reduced 8–13% ( P < 0.05) after 8 wk of OVX compared with sham in WT mice. As expected, total body, femur, and lumbar BMD were reduced 14–21% ( P < 0.05) in Cldn-18 KO sham mice compared with sham WT mice. However, ovariectomy failed to induce significant changes in BMD of total body, femur, or vertebra in the Cldn-18 KO mice. μCT analysis of the distal femur revealed that trabecular (Tb) bone volume was decreased 50% in the OVX WT mice compared with sham that was caused by a 26% decrease in Tb number and a 30% increase in Tb separation (all P < 0.05). By contrast, none of the Tb parameters were significantly different in OVX Cldn-18 KO mice compared with sham KO mice. Histomorphometric analyses at the Tb site revealed that neither osteoclast surface nor osteoclast perimeter was increased significantly as a consequence of OVX in either genotype at the time point examined. Based on our findings, we conclude that the estrogen effects on osteoclasts may in part be mediated via regulation of Cldn-18 signaling.

scholarly journals Alternative regulatory mechanism for the maintenance of bone homeostasis via STAT5-mediated regulation of the differentiation of BMSCs into adipocytes

2021 ◽  
Author(s):  
Semun Seong ◽  
Jung Ha Kim ◽  
Kabsun Kim ◽  
Inyoung Kim ◽  
Jeong-Tae Koh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Loss ◽  
Target Genes ◽  
Osteoclast Differentiation ◽  
Conditional Knockout ◽  
Negative Regulator ◽  
Bone Homeostasis

AbstractSTAT5 is a transcription factor that is activated by various cytokines, hormones, and growth factors. Activated STAT5 is then translocated to the nucleus and regulates the transcription of target genes, affecting several biological processes. Several studies have investigated the role of STAT5 in adipogenesis, but unfortunately, its role in adipogenesis remains controversial. In the present study, we generated adipocyte-specific Stat5 conditional knockout (cKO) (Stat5fl/fl;Apn-cre) mice to investigate the role of STAT5 in the adipogenesis of bone marrow mesenchymal stem cells (BMSCs). BMSC adipogenesis was significantly inhibited upon overexpression of constitutively active STAT5A, while it was enhanced in the absence of Stat5 in vitro. In vivo adipose staining and histological analyses revealed increased adipose volume in the bone marrow of Stat5 cKO mice. ATF3 is the target of STAT5 during STAT5-mediated inhibition of adipogenesis, and its transcription is regulated by the binding of STAT5 to the Atf3 promoter. ATF3 overexpression was sufficient to suppress the enhanced adipogenesis of Stat5-deficient adipocytes, and Atf3 silencing abolished the STAT5-mediated inhibition of adipogenesis. Stat5 cKO mice exhibited reduced bone volume due to an increase in the osteoclast number, and coculture of bone marrow-derived macrophages with Stat5 cKO adipocytes resulted in enhanced osteoclastogenesis, suggesting that an increase in the adipocyte number may contribute to bone loss. In summary, this study shows that STAT5 is a negative regulator of BMSC adipogenesis and contributes to bone homeostasis via direct and indirect regulation of osteoclast differentiation; therefore, it may be a leading target for the treatment of both obesity and bone loss-related diseases.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Anti-obesity role of Aster glehni extract: in vivo and in vitro effects

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Lee ◽  
TG Ahn ◽  
CW Kim ◽  
HJ An
Keyword(s):  
In Vitro Effects

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

THYROID STIMULATORS AND THYROID STIMULATION

1971 ◽  
Vol 66 (3) ◽  
pp. 558-576 ◽  
Author(s):  
Gerald Burke
Keyword(s):  
Regulatory System ◽  
Control Site ◽  
Thyroid Cell ◽  
Primary Control ◽  
Physico Chemical ◽  
Site Of Action ◽  
Long Acting

ABSTRACT A long-acting thyroid stimulator (LATS), distinct from pituitary thyrotrophin (TSH), is found in the serum of some patients with Graves' disease. Despite the marked physico-chemical and immunologic differences between the two stimulators, both in vivo and in vitro studies indicate that LATS and TSH act on the same thyroidal site(s) and that such stimulation does not require penetration of the thyroid cell. Although resorption of colloid and secretion of thyroid hormone are early responses to both TSH and LATS, available evidence reveals no basic metabolic pathway which must be activated by these hormones in order for iodination reactions to occur. Cyclic 3′, 5′-AMP appears to mediate TSH and LATS effects on iodination reactions but the role of this compound in activating thyroidal intermediary metabolism is less clear. Based on the evidence reviewed herein, it is suggested that the primary site of action of thyroid stimulators is at the cell membrane and that beyond the(se) primary control site(s), there exists a multifaceted regulatory system for thyroid hormonogenesis and cell growth.

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