scholarly journals Sclareol prevents ovariectomy-induced bone loss in vivo and inhibits osteoclastogenesis in vitro via suppressing NF-κB and MAPK/ERK signaling pathways

2019 ◽  
Vol 10 (10) ◽  
pp. 6556-6567 ◽  
Author(s):  
Haiming Jin ◽  
Zhenxuan Shao ◽  
Qingqing Wang ◽  
Jiansen Miao ◽  
Xueqin Bai ◽  
...  

Postmenopausal osteoporosis (PMO) is a progressive disease occurring in elderly postmenopausal women that is characterized by low bone mass and impaired bone quality.

2017 ◽  
Vol 3 (4) ◽  
pp. 12-16
Author(s):  
Edwin Antonio Wandurraga ◽  
Lisseth Fernanda Marín Carrillo ◽  
Annie Katherine Natera Melo ◽  
Claudia Milena Gómez Giraldo ◽  
Juan Camilo Mendoza Díaz

Introducción: La osteoporosis posmenopáusica puede coexistir con otras entidades que aumentan la pérdida ósea.Objetivo: Determinar la frecuencia de causas secundarias de baja masa ósea en mujeres con osteoporosis posmenopáusica en una población colombiana.Diseño: Estudio descriptivo retrospectivo.Población: Mujeres mayores de 50 años con diagnóstico reciente de osteoporosis posmenopáusica antes de iniciar tratamiento.Mediciones: Se incluyeron variables demográficas, densitométricas y bioquímicas como hemoglobina, fosfatasa alcalina, transaminasas, creatinina, 25-hidroxivitamina D, calcio, fósforo, magnesio, calciuria en 24 horas, PTH y TSH.Resultados: Se incluyeron 129 mujeres con edad promedio de 67+/-8,8 años. Cuarenta y nueve mujeres (36%) presentaban antecedente de fractura por fragilidad. En el 86,8% se encontró al menos una alteración bioquímica asociada con pérdida de masa ósea, documentándose insuficiencia de vitamina D en 71,8%, hiperparatiroidismo normocalcémico en 18,1% e hipercalciuria en 6,4%. Las mujeres con antecedente de fractura presentaron valor promedio de fosfatasa alcalina superior (111,6 +/- 61,3 vs 87,1 +/- 30,4 U/L, p= 0,0143) y promedio de hemoglobina inferior (12,9 +/- 1,2 vs. 14,2 +/- 1,2gr/dl, p<0,0001) al compararse con las mujeres sin fractura. Se encontró correlación inversa entre los niveles de fosfatasa alcalina y la densidad mineral ósea de la columna lumbar (p<0,001) y la cadera (p=0,003).Conclusiones: Las causas secundarias de baja masa ósea en mujeres con OPM son frecuentes en nuestro medio. Con base en una frecuencia de alteraciones mayor al 5%, sugerimos la evaluación de toda mujer con OPM con hemoglobina, calcio, calciuria en 24 horas, 25-hidroxivitamina D, AST, PTH y TSH.Abstract Introduction: Postmenopausal osteoporosis can coexist with other entities that increase bone loss. Aim: To determine the frequency of secondary causes of low bone mass in women with postmenopausal osteoporosis in a Colombian population. Materials and methods: A retrospective descriptive study was conducted, including women over 50 years with newly diagnosed postmenopausal osteoporosis without treatment. Demographic, densitometric and biochemical variables such as hemoglobin, alkaline phosphatase, transaminases, creatinine, 25 hydroxivitamin D, calcium, phosphorus, magnesium, calciuria in 24 hours, PTH and TSH were evaluated.Results: 129 women with a mean age of 67 +/- 8,8 years were included. 49 patients (36%) had history of fragility fracture. At least one biochemical disorder associated with bone loss was reported in 86,8% of cases, vitamin D insufficiency was documented in 71,8%, normocalcemic hyperparathyroidism in 18,1% and hypercalciuria in 6,4%. Women with history of fracture showed higher average value of alkaline phosphatase (111,6 +/- 61,3 vs 87,1 +/- 30,4 U/L, p=0,0143) and lower mean hemoglobin (12,9 +/- 1,2 vs 14,2 +/- 1,2 gr/dl, p<0,0001) compared with women without fracture. Inverse correlation was found between levels of alkaline phosphatase and bone mineral density of lumbar spine (p<0,001) and hip (p=0,003). Conclusions: Secondary causes of low bone mass in women with PMO are frequent in our clinical practice. Based on a frequency of laboratory abnormalities greater than 5%, we suggest that all women with PMO should be studied with hemoglobin, serum calcium, urinary calcium in 24 hours, 25 hydroxivitamin D, AST, PTH and TSH. Keywords: ; ; etiology;; .


1997 ◽  
Vol 7 (2) ◽  
pp. 119-125 ◽  
Author(s):  
S. Adami ◽  
L. Bufalino ◽  
R. Cervetti ◽  
C. Di Marco ◽  
O. Di Munno ◽  
...  

2020 ◽  
Vol 4 (3) ◽  
pp. 351-357
Author(s):  
Sanusi Bello Mada ◽  
Philip Cefas Abaya ◽  
Dorcas Bolanle James ◽  
Muawiya Musa Abarshi ◽  
Muhammad Said Tanko

Postmenopausal osteoporosis is a global health problem characterized by decreased in bone mineral density (BMD) and progressive deterioration of microarchitecture and subsequent increase in bone fragility and susceptibility to fracture.  More than 200 million people suffer from osteoporosis worldwide  with about 8.9 million fractures and the prevalence rate of osteoporosis is expected to increase significantly in the future because of increased in life expectancy and aging population. Milk-derived bioactive peptides from cow, goat, sheep, buffalo, and camel exhibit several potential health promoting effect including antiosteoporosis, antihypertensive, antioxidative, antithrombotic, immunomodulatory and anti-inflammatory effects. Epidemiological and intervention studies have shown that milk and milk-derived peptides prevented bone loss in pre- and postmenopausal women. Moreover, quite a lot of studies have reported that milk-derived bioactive peptides can induce osteoblast cell proliferation, differentiation and also prevented bone loss in osteoporotic rats model. Thus, milk-derived peptides exhibits beneficial effect against bone-related diseases and can be of particular interest towards prevention and management of postmenopausal osteoporosis. Hence, the present review summarizes various studies using ISI, SCOPUS and PubMed indexed journals to elucidate the potential role of milk-derived bioactive peptides with in vitro and in vivo antiosteoporotic property


2021 ◽  
Vol 12 ◽  
Author(s):  
Gaoran Ge ◽  
Sen Yang ◽  
Zhenyang Hou ◽  
Minfeng Gan ◽  
Huaqiang Tao ◽  
...  

Postmenopausal osteoporosis is a disease of bone mass reduction and structural changes due to estrogen deficiency, which can eventually lead to increased pain and fracture risk. Chronic inflammatory microenvironment leading to the decreased activation of osteoblasts and inhibition of bone formation is an important pathological factor that leads to osteoporosis. Theaflavin-3,3′-digallate (TFDG) is an extract of black tea, which has potential anti-inflammatory and antiviral effects. In our study, we found that TFDG significantly increased the bone mass of ovariectomized (OVX) mice by micro-CT analysis. Compared with OVX mice, TFDG reduced the release of proinflammatory cytokines and increased the expression of osteogenic markers in vivo. In vitro experiments demonstrated that TFDG could promote the formation of osteoblasts in inflammatory environment and enhance their mineralization ability. In this process, TFDG activated MAPK, Wnt/β-Catenin and BMP/Smad signaling pathways inhibited by TNF-α, and then promoted the transcription of osteogenic related factors including Runx2 and Osterix, promoting the differentiation and maturation of osteoblasts eventually. In general, our study confirmed that TFDG was able to promote osteoblast differentiation under inflammatory environment, enhance its mineralization ability, and ultimately increase bone mass in ovariectomized mice. These results suggested that TFDG might have the potential to be a more effective treatment of postmenopausal osteoporosis.


2004 ◽  
Vol 49 (12) ◽  
Author(s):  
U Boudriot ◽  
B Daume ◽  
J Brandt

AbstractNeuere Forschungsergebnisse zeigen, daß die mechanische Belastung als einer der wesentlichen Faktoren zur Beeinflussung des Knochenstoffwechsels angesehen werden kann. In vivo Untersuchungen ebenso wie Methoden der Zellkultur trugen zum besseren Verständnis der Knochenauf- und Umbauprozesse bei. Die genauen Mechanismen wie der belastungsinduzierte Knochenstoffwechsel reguliert wird, konnten jedoch bisher nicht vollständig geklärt werden. Das Prinzip, daß mechanische Belastung innerhalb physiologischer Grenzen den Knochenaufbau stimuliert und Entlastung zu einem Knochenverlust führt, wird allgemein anerkannt. Bisher konnte jedoch weder ein Schwellenwert noch die wirksame Form eines mechanischen Reizes definiert werden. Noch unsicherer sind die Erkenntnisse darüber, auf welche Weise das Signal des mechanischen Reizes den Knochenstoffwechsel reguliert. Dreidimensionale Knochenorgan- Perfusionskulturen mit gleichzeitig applizierter mechanischer Belastung bieten die Möglichkeit, die Regulation des Knochenstoffwechsels besser zu verstehen. Wir zeigen die Ergebnisse eines Langzeitversuches mit humanem, spongiösem Knochen unter physiologischen Lastbedingungen in vitro. There is evidence that mechanical loading is an important, if not the most important factor influencing bone mass and architecture. Investigations under in vivo conditions and cell culture methods, performed during the last years, helped to elucidate these mechanisms. However, the mechanisms by whitch load bearing acts on bone tissue are until now not completely understood. It is well accepted that weight-bearing exercise increases bone mass and on the other hand lower physical activity engenders bone loss. But neither a physiological threshold for bone loss or bone growth nor the character of the mechanical stimulus concerning amount, frequency and duration of the applied load are known. Even more speculative is the idea how this signal is transformed into the biological respons of growing bone. Three- dimensional bone- culture- systems with simultaneous applied mechanical load enables to improve the knowledge of regulation of bone metabolism. We show the results of a long- term in vitro experiment with human cancellous bone under physiological load conditions.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Gyhye Yoo ◽  
Ji-Hye Park ◽  
Yang-Ju Son ◽  
Chang Ho Lee ◽  
Chu Won Nho

Abstract Objectives Postmenopausal osteoporosis, a condition of low bone density consequent to decreased estrogen levels after menopause in women, is generally treated with hormone replacement therapy. However, long-term hormone use may cause critical side effects including breast cancer. Alternatively, phytoestrogens, which have similar structures to steroid hormones, are reported to cure postmenopausal symptoms with fewer side effects. Here, we investigated the effects of EtOH extract of Circaea mollis Siebold & Zucc. (EECM), a traditional herbal medicine in Asia that exhibits anti-arthritic activities, on postmenopausal osteoporosis. Methods In vitro model: MCF7 breast cancer cells and MC3T3-E1 pre-osteoblast cells were utilized to estimate estrogenic and osteogenic activity. Osteoblastic markers were measured by western blot and real-time PCR. In vivo model: Female mature C57BL/6 mice were ovariectomized and oral administrated with 10 mg/kg and 40 mg/kg of EECM respectively. Results EECM increased alkaline phosphatase activity and osteoblastic markers including osteoprotegerin at day 6 during mouse preosteoblast differentiation. EECM inhibited osteoclast differentiation and bone resorption in an osteoblast-osteoclast primary co-culture system via osteoprotegerin-mediated RANK/RANKL signaling. In ovariectomized mice, EECM prevented bone mineral density decrease and recovered osteoblastic molecules. Conclusions EECM enhanced the differentiation of osteoblasts via osteogenic markers and modulated RANK/RANKL signaling via an elevation of OPG from osteoblasts in vitro and in vivo. Therefore, EECM may be effective in preventing bone loss and offers a promising alternative for the nutritional management of postmenopausal osteoporosis. Funding Sources This work was supported by the Center Project for the Korea-Mongolia Science and Technology Cooperation (2U06170). Supporting Tables, Images and/or Graphs


2001 ◽  
Vol 12 (3) ◽  
pp. 252-261 ◽  
Author(s):  
Peter M. Loomer

Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. In-flight measures used to counteract this, including intensive daily exercise regimens, have been only partially successful in reducing the bone loss and in the process have consumed valuable work time. If this bone loss is to be minimized or, preferably, prevented, more effective treatment strategies are required. This, however, requires a greater understanding of the mechanisms through which bone metabolism is affected by microgravity. Various research strategies have been used to examine this problem, including in vitro studies using bone cells and in vivo studies on humans and rats. These have been conducted both in flight and on the ground, by strategies that produce weightlessness to mimic the effects of microgravity. Overall, the majority of the studies have found that marked decreases in gravitation loading result in the loss of bone mass. The processes of bone formation and bone resorption become uncoupled, with an initial transitory increase in resorption accompanied by a prolonged decrease in formation. Loss of bone mass is not uniform throughout the skeleton, but varies at different sites depending on the type of bone and on the mechanical load received. It appears that the skeletal response is a physiologic adaptation to the space environment which, after long space flights or repeated shorter ones, could eventually lead to significant reductions in the ability of the skeletal tissues to withstand the forces of gravity and increased susceptibility to fracture.


Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2141-2149 ◽  
Author(s):  
Antonia Sophocleous ◽  
Euphemie Landao-Bassonga ◽  
Robert J. van‘t Hof ◽  
Aymen I. Idris ◽  
Stuart H. Ralston

The type 2 cannabinoid receptor (CB2) has been reported to regulate bone mass and bone turnover but the mechanisms responsible are incompletely understood. In this study we investigated the role that the CB2 pathway plays in bone metabolism using a combination of genetic and pharmacological approaches. Bone mass and turnover were normal in young mice with targeted inactivation of CB2 receptor (CB2−/−), but by 12 months of age, they had developed high-turnover osteoporosis with relative uncoupling of bone resorption from bone formation. Primary osteoblasts from CB2−/− mice had a reduced capacity to form bone nodules in vitro when compared with cells from wild-type littermates and also had impaired PTH-induced alkaline phosphatase (ALP) activity. The CB2-selective agonist HU308 stimulated bone nodule formation in wild-type osteoblasts but had no effect in CB2−/− osteoblasts. Further studies in MC3T3-E1 osteoblast like cells showed that HU308 promoted cell migration and activated ERK phosphorylation, and these effects were blocked by the CB2 selective inverse agonist AM630. Finally, HU308 partially protected against ovariectomy induced bone loss in wild-type mice in vivo, primarily by stimulating bone formation, whereas no protective effects were observed in ovariectomized CB2−/− mice. These studies indicate that the CB2 regulates osteoblast differentiation in vitro and bone formation in vivo.


2004 ◽  
Vol 164 (4) ◽  
pp. 509-514 ◽  
Author(s):  
Romain Dacquin ◽  
Rachel A. Davey ◽  
Catherine Laplace ◽  
Régis Levasseur ◽  
Howard A. Morris ◽  
...  

Amylin is a member of the calcitonin family of hormones cosecreted with insulin by pancreatic β cells. Cell culture assays suggest that amylin could affect bone formation and bone resorption, this latter function after its binding to the calcitonin receptor (CALCR). Here we show that Amylin inactivation leads to a low bone mass due to an increase in bone resorption, whereas bone formation is unaffected. In vitro, amylin inhibits fusion of mononucleated osteoclast precursors into multinucleated osteoclasts in an ERK1/2-dependent manner. Although Amylin +/− mice like Amylin-deficient mice display a low bone mass phenotype and increased bone resorption, Calcr +/− mice display a high bone mass due to an increase in bone formation. Moreover, compound heterozygote mice for Calcr and Amylin inactivation displayed bone abnormalities observed in both Calcr +/− and Amylin +/− mice, thereby ruling out that amylin uses CALCR to inhibit osteoclastogenesis in vivo. Thus, amylin is a physiological regulator of bone resorption that acts through an unidentified receptor.


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