scholarly journals Estrogen receptor alpha, but not estrogen receptor beta, is involved in the regulation of the OPG/RANKL (osteoprotegerin/receptor activator of NF-kappa B ligand) ratio and serum interleukin-6 in male mice

2001 ◽  
Vol 171 (3) ◽  
pp. 425-433 ◽  
Author(s):  
MK Lindberg ◽  
M Erlandsson ◽  
SL Alatalo ◽  
S Windahl ◽  
G Andersson ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Interleukin 6 ◽  
Serum Levels ◽  
Tartrate Resistant Acid Phosphatase ◽  
Male Mice ◽  
Mineral Density ◽  
Nf Kappa B ◽  
Receptor Activator ◽  
Trap 5B ◽  
Er Alpha

Estrogens are important for the male skeleton. Osteoprotegerin (OPG), receptor activator of NF-kappa B ligand (RANKL), interleukin-6 (IL-6), IL-1 and tumor necrosis factor alpha (TNFalpha) have been suggested to be involved in the skeletal effects of estrogen. We treated orchidectomized mice with estradiol for 2 weeks and observed a 143% increase in the trabecular bone mineral density of the distal metaphysis of femur that was associated with a decreased OPG/RANKL mRNA ratio in vertebral bone. A similar decreased OPG/RANKL ratio was also seen after estrogen treatment of ovariectomized female mice. The effect of estrogen receptor (ER) inactivation on the OPG/RANKL ratio was dissected by using intact male mice lacking ER alpha (ERKO), ER beta (BERKO) or both receptors (DERKO). The expression of OPG was increased in ERKO and DERKO but not in BERKO male mice, resulting in an increased OPG/RANKL ratio. Furthermore, serum levels of IL-6 and tartrate-resistant acid phosphatase 5b (TRAP 5b) were decreased in ERKO and DERKO, but not in BERKO male mice. These results demonstrate that ER alpha, but not ER beta, is involved in the regulation of the vertebral OPG/RANKL ratio, serum levels of IL-6 and TRAP 5b in male mice.

scholarly journals Effect of Intermittent Fasting on Glucose Homeostasis and Bone Remodeling in Glucocorticoid-Induced Osteoporosis Rat Model

2021 ◽  
Vol 28 (4) ◽  
pp. 307-316
Author(s):  
Majed G. Alrowaili ◽  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Mohamed S. Serria ◽  
Hussein Abdellatif ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Bone Mineral ◽  
Serum Levels ◽  
Male Rats ◽  
Control Group ◽  
Intermittent Fasting ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Mineral Density ◽  
Trap 5B

Background: The present study examined the effect of intermittent fasting (IF) on bone mineral content (BMC) and bone mineral density (BMD) and the markers of bone remodeling in a glucocorticoid-induced osteoporosis (GIO) rat model.Methods: Forty male rats were allocated to 4 groups (N=10 per group): control group of normal rats; control+IF group (normal rats subjected to IF for 16-18 hr daily for 90 days); dexamethasone (DEX) group: (DEX [0.5 mg i.p.] for 90 days); and DEX+IF group (DEX and IF for 90 days). By the end of the experiment, BMD and BMC in the right tibia were measured. Serum levels of the following were measured: glucose; insulin; triglycerides (TGs); total cholesterol; parathyroid hormone (PTH); osteoprotegerin (OPG); receptor activator of nuclear factor-κB (RANK); bone-resorbing cytokines, including bone deoxypyridinoline (DPD), N-terminal telopeptide of collagen type I (NTX-1), and tartrate-resistant acid phosphatase 5b (TRAP-5b); and bone-forming cytokines, including alkaline phosphatase (ALP) and osteocalcin (OC).Results: DEX administration for 90 days resulted in significantly increased serum levels of glucose, insulin, TGs, cholesterol, PTH, OPG, DPD, NTX-1, and TRAP-5b and significantly decreased BMD, BMC, and serum levels of RANK, OC, and ALP (all P<0.05). IF for 90 days significantly improved all these parameters (all P<0.05).Conclusions: IF corrected GIO in rats by inhibiting osteoclastogenesis and PTH secretion and stimulating osteoblast activity.

Membrane estrogen receptor α is essential for estrogen signaling in the male skeleton

2018 ◽  
Vol 239 (3) ◽  
pp. 303-312 ◽  
Author(s):  
H H Farman ◽  
K L Gustafsson ◽  
P Henning ◽  
L Grahnemo ◽  
V Lionikaite ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Areal Bone Mineral Density ◽  
Male Mice ◽  
Mineral Density ◽  
Intact Male ◽  
Trabecular Thickness ◽  
Total Body

The importance of estrogen receptor α (ERα) for the regulation of bone mass in males is well established. ERα mediates estrogenic effects both via nuclear and membrane-initiated ERα (mERα) signaling. The role of mERα signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERα signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ERα to the plasma membrane. Gonadal-intact male NOER mice had a significantly decreased total body areal bone mineral density (aBMD) compared to WT littermates at 3, 6 and 9 months of age as measured by dual-energy X-ray absorptiometry (DEXA). High-resolution microcomputed tomography (µCT) analysis of tibia in 3-month-old males demonstrated a decrease in cortical and trabecular thickness in NOER mice compared to WT littermates. As expected, estradiol (E2) treatment of orchidectomized (ORX) WT mice increased total body aBMD, trabecular BV/TV and cortical thickness in tibia compared to placebo treatment. E2 treatment increased these skeletal parameters also in ORX NOER mice. However, the estrogenic responses were significantly decreased in ORX NOER mice compared with ORX WT mice. In conclusion, mERα is essential for normal estrogen signaling in both trabecular and cortical bone in male mice. Increased knowledge of estrogen signaling mechanisms in the regulation of the male skeleton may aid in the development of new treatment options for male osteoporosis.

scholarly journals Estrogen receptor specificity in the regulation of the skeleton in female mice

2001 ◽  
Vol 171 (2) ◽  
pp. 229-236 ◽  
Author(s):  
MK Lindberg ◽  
SL Alatalo ◽  
JM Halleen ◽  
S Mohan ◽  
JA Gustafsson ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Bone Growth ◽  
Fat Content ◽  
Mineral Density ◽  
Trabecular Bone Mineral Density ◽  
Longitudinal Bone Growth ◽  
Female Mice ◽  
Opposing Effects ◽  
Er Alpha

There are two known estrogen receptors, estrogen receptor-alpha (ER alpha) and estrogen receptor-beta (ER beta), which may mediate the actions of estrogen. The aim of the present study was to compare fat content, skeletal growth and adult bone metabolism in female mice lacking ER alpha (ERKO), ER beta (BERKO) or both ERs (DERKO). We demonstrate that endogenous estrogens decrease the fat content in female mice via ER alpha and not ER beta. Interestingly, the longitudinal bone growth was decreased in ERKO, increased in BERKO, but was intermediate in DERKO females, demonstrating that ER alpha and ER beta exert opposing effects in the regulation of longitudinal bone growth. The effects on longitudinal bone growth were correlated with similar effects on serum levels of IGF-I. A complex regulation of the trabecular bone mineral density (BMD), probably caused by a disturbed feedback regulation of estrogen and testosterone, was observed in female ER-inactivated mice. Nevertheless, a partial functional redundancy for ER alpha and ER beta in the maintenance of the trabecular BMD was observed in the female mice at 60 days of age. Thus, ER alpha and ER beta may have separate effects (regulation of fat), opposing effects (longitudinal bone growth) or partial redundant effects (trabecular BMD at 60 days of age), depending on which parameter is studied.

scholarly journals Effects of Rambutan Peel (Nepheliumlappaceum) PhenolicExtract on RANKL-Induced Differentiation of RAW264.7 Cells into Osteoclasts and Retinoic Acid-Induced Osteoporosis in Rats

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 883 ◽  
Author(s):  
Yongliang Zhuang ◽  
Xiaodong Sun ◽  
Bingtong Liu ◽  
Hu Hou ◽  
Yun Sun
Keyword(s):  
Cortical Bone ◽  
Biological Activities ◽  
Maximum Load ◽  
Serum Levels ◽  
Raw264.7 Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Induced Differentiation ◽  
Potential Applications ◽  
Calcium Loss

Previous studies have shown that rambutan peel phenolic (RPP) extract has excellent biological activities due to its abundant phenolic content and profile. In this study, the potential anti-osteoporosis (OP) effects of RPP were evaluated by suppressing receptor activator nuclear factor-kappa B ligand (RANKL)-induced differentiation of RAW264.7 cells into osteoclasts and amelioratingretinoic acid-induced OP in rats. Our results showed that RPP efficiently decreased the formation of tartrate-resistant acid phosphatase (TRAP)-positive cells and reduced total TRAP activity in RAW264.7 cells under RANKL stimulation. RPP treatment significantlyameliorated retinoid acid-induced calcium loss in rats (p < 0.05). The serum phosphorus level of osteoporotic rats was increased by RPP treatment, and the serum levels of total alkaline phosphatase and osteocalcin in osteoporotic rats were further reduced. RPP treatment improved the qualities of the femur and tibia, such asbone mineral density, bone length, bone maximum load, cortical bone area ratio, and trabecularelative bone density in osteoporotic rats to some extent. Furthermore, histological analysis showed that RPP effectively improved the bone microstructure of osteoporotic rats by regulating the cortical bone thickness and trabecular bone separation. These results indicate that RPP could have potential applications as a newnutraceutical and functional food in the prevention of OP.

scholarly journals Serum Heme Oxygenase-1 and BMP-7 Are Potential Biomarkers for Bone Metabolism in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Tong-ling Yuan ◽  
Jin Chen ◽  
Yan-li Tong ◽  
Yan Zhang ◽  
Yuan-yuan Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Bone Metabolism ◽  
Bone Remodeling ◽  
Heme Oxygenase ◽  
Serum Levels ◽  
Heme Oxygenase 1 ◽  
Tartrate Resistant Acid Phosphatase ◽  
Trap 5B ◽  
Potential Biomarkers

Backgrounds. Heme oxygenase-1 (HO-1) has been reported to play a regulatory role in osteoclastogenesis. Bone morphogenetic protein (BMP) pathways induce osteoblastic differentiation and bone remodeling.Aims. To identify serum levels of HO-1, BMP-7, and Runt related-transcription factor 2 (Runx2) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to investigate the relationships between HO-1, BMP-7, Runx2, and other common biomarkers for bone metabolism.Results. Serum levels of HO-1 and BMP-7 were revealed to be significantly higher in patients with RA or AS than in healthy controls (p<0.01). In RA group, HO-1 was positively correlated with BMP-7, Runx2, and tartrate-resistant acid phosphatase-5b (TRAP-5b) (p<0.05, resp.), BMP-7 was positively correlated with Runx2 and TRAP-5b (p<0.05, resp.), and Runx2 was negatively correlated with N-terminal midfragment of osteocalcin (NMID) (p<0.05). In AS group, we observed identical correlation between HO-1 and BMP-7, but opposite correlations between BMP-7 and TRAP-5b and between Runx2 and NMID, when comparing with the RA cohort.Conclusion. Our findings suggest that HO-1 and BMP-7 are potential biomarkers for bone metabolism in patients with RA and AS. The different correlations between the bone markers point to distinct differences in bone remodeling pathways in the two types of arthritis.

scholarly journals Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta.

1995 ◽  
Vol 15 (9) ◽  
pp. 4971-4979 ◽  
Author(s):  
B Stein ◽  
M X Yang
Keyword(s):  
Estrogen Receptor ◽  
Bone Resorption ◽  
Interleukin 6 ◽  
Binding Sites ◽  
Hormone Replacement ◽  
Direct Interaction ◽  
Nf Kappa B ◽  
Two Factors

Bone metabolism is regulated by a balance between bone resorption caused by osteoclasts and bone formation caused by osteoblasts. This balance is disturbed in postmenopausal women as a result of lower serum estrogen levels. Estrogen, which is used in hormone replacement therapy to prevent postmenopausal osteoporosis, downregulates expression of the interleukin 6 (IL-6) gene in osteoblasts and bone marrow stromal cells. IL-6 is directly involved in bone resorption by activating immature osteoclasts. We show here that NF-kappa B and C/EBP beta are important regulators of IL-6 gene expression in human osteoblasts. Importantly, the IL-6 promoter is inhibited by estrogen in the absence of a functional estrogen receptor (ER) binding site. This inhibition is mediated by the transcription factors NF-kappa B and C/EBP beta. Evidence is presented for a direct interaction between these two factors and ER. We characterized the protein sequence requirements for this association in vitro and in vivo. The physical and functional interaction depends in part on the DNA binding domain and region D of ER and on the Rel homology domain of NF-kappa B and the bZIP region of C/EBP beta. The cross-coupling between ER, NF-kappa B, and C/EBP beta also results in reduced activity of promoters with ER binding sites. We further show that the mechanism of IL-6 gene repression by estrogen is clearly different from that of activation of promoters with ER binding sites. Therefore, drugs that separate the transactivation and transrepression functions of ER will be very helpful for treatment of osteoporosis without causing undesirable side effects.

scholarly journals Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta

2003 ◽  
pp. 351-362 ◽  
Author(s):  
D Seidlova-Wuttke ◽  
O Hesse ◽  
H Jarry ◽  
V Christoffel ◽  
B Spengler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Selective Estrogen Receptor Modulator ◽  
Ovariectomized Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Complement Protein ◽  
Cimicifuga Racemosa ◽  
Mineral Density ◽  
Receptor Modulator ◽  
Igf I

OBJECTIVE: Some phytoestrogens are believed to have selective estrogen receptor modulator (SERM) activity with no action in the uterus but beneficial effects in the hypothalamo/pituitary unit and in the bone and are presently the focus of clinical interest. In the present experiments, the effects of the clinically used Cimicifuga racemosa (CR) extract BNO 1055 in the uterus, in the bone and on serum luteinizing hormone (LH) were compared with the effects of estradiol-17beta (E(2)) under acute and chronic conditions in ovariectomized rats. METHODS: Ovariectomized rats were treated either acutely (6 h) or chronically (3 Months) with E(2) or the CR extract. Gene expression of some estrogen-regulated genes in the metaphysis of the tibia and the uterus was determined. Furthermore, bone mineral density was measured by quantitative computer tomography. RESULTS: When given acutely, both E(2) and the CR extract inhibited LH secretion and slightly stimulated gene expression of IGF-I, collagen-1alpha1, osteoprotegerin and osteocalcin (all osteoblast products), and of tartrate-resistant acid phosphatase (TRAP, an osteoclast product) in the metaphysis of the femur. While E(2) stimulated uterine weight and expression of progesterone receptor (PR), the complement protein (C3) and IGF-I genes, and inhibited gene expression of the estrogen receptor beta (ERbeta) in the uterus, no such effect was observed under acute CR treatment. After chronic application with pelleted food over 3 Months E(2) had profound effects in the uterus on weight and gene expression (ERbeta, PR, C3 and IGF-I) which were not seen in the CR-treated animals. Within 3 Months after ovariectomy, control rats had lost more than 50% of the metaphyseal bone mass of the tibia, an effect prevented by E(2) and partially by CR supplementation. CONCLUSIONS: These data confirm the concept that the CR extract BNO 1055 contains as yet unidentified substances with SERM properties which act in the hypothalamo/pituitary unit and in the bone but not in the uterus.

scholarly journals Persistent increase of osteoprotegerin levels after cortisol normalization in patients with Cushing's syndrome

2010 ◽  
Vol 162 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Valentina Camozzi ◽  
Francesca Sanguin ◽  
Nora Albigier ◽  
Carla Scaroni ◽  
Franco Mantero ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Cushing’S Syndrome ◽  
Osteoclast Differentiation ◽  
Serum Levels ◽  
Cushing's Syndrome ◽  
Mineral Density ◽  
Receptor Activator ◽  
Before And After ◽  
Design And Methods ◽  
Gonadal Status

ObjectiveOsteoprotegerin (OPG) has been identified as a decoy receptor that inhibits osteoclast differentiation and, more recently, as a paracrine regulator of vascular calcification. OPG is suppressed by glucocorticoids (GC); however, results from experimental and clinical studies are not univocal. The aim of this study was to evaluate OPG and bone metabolism in patients with Cushing's syndrome (CS) before and after cure.Design and methodsTwenty-six patients with CS (all women, mean age: 39.1±11.9 years) and 24 age- and gonadal status-matched healthy women were studied for bone mineral density, bone metabolism, OPG, and receptor activator of nuclear factor-kB ligand at baseline. Twelve patients were also studied 6–18 months after surgery, with persistent normalization of cortisol levels.ResultsOPG was significantly higher and osteocalcin (OC) was significantly lower in CS patients than in controls (OPG: 4.17±1.23 vs 2.95±0.79 pmol/l, P=0.00001; OC: 15.0±6.1 vs 18.8±6.8 ng/ml, P=0.04 in CS and controls respectively). After cure, we found no difference in OPG levels, despite a significant increase in OC levels (from 16.4±11 to 37.2±15 ng/ml, P=0.03).ConclusionPatients with CS showed increased OPG serum levels that remained unchanged after recovery, despite a restoration of bone formation. We speculate that high levels of OPG could reflect the persistent damage of the GCs on cardiovascular system.

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