scholarly journals Protective Effects of 2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside on Ovariectomy Induced Osteoporosis Mouse Model

2018 ◽  
Vol 19 (9) ◽  
pp. 2554 ◽  
Author(s):  
Su-Jin Kim ◽  
Yun-Ho Hwang ◽  
Seul-Ki Mun ◽  
Seong-Gyeol Hong ◽  
Kwang-Jin Kim ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Loss ◽  
Cell Damage ◽  
Bone Destruction ◽  
Tartrate Resistant Acid Phosphatase ◽  
Protective Effects ◽  
Micro Computed Tomography ◽  
Aging Effects ◽  
Polygonum Multiflorum ◽  
Ovariectomized Mice

2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG), an active polyphenolic component of Polygonum multiflorum, exhibits many pharmacological activities including antioxidant, anti-inflammation, and anti-aging effects. A previous study demonstrated that TSG protected MC3T3-E1 cells from hydrogen peroxide (H2O2) induced cell damage and the inhibition of osteoblastic differentiation. However, no studies have investigated the prevention of ovariectomy-induced bone loss in mice. Therefore, we investigated the effects of TSG on bone loss in ovariectomized mice (OVX). Treatment with TSG (1 and 3 μg/g; i.p.) for six weeks positively affected body weight, uterine weight, organ weight, bone length, and weight change because of estrogen deficiency. The levels of the serum biochemical markers of calcium (Ca), inorganic phosphorus (IP), alkaline phosphatase (ALP), and total cholesterol (TCHO) decreased in the TSG-treated mice when compared with the OVX mice. Additionally, the serum bone alkaline phosphatase (BALP) levels in the TSG-treated OVX mice were significantly increased compared with the OVX mice, while the tartrate-resistant acid phosphatase (TRAP) activity was significantly reduced. Furthermore, the OVX mice treated with TSG showed a significantly reduced bone loss compared to the untreated OVX mice upon micro-computed tomography (CT) analysis. Consequently, bone destruction in osteoporotic mice as a result of ovariectomy was inhibited by the administration of TSG. These findings indicate that TSG effectively prevents bone loss in OVX mice; therefore, it can be considered as a potential therapeutic for the treatment of postmenopausal osteoporosis.

scholarly journals Constitutive Activation of β-Catenin in Differentiated Osteoclasts Induces Bone Loss in Mice

2018 ◽  
Vol 48 (5) ◽  
pp. 2091-2102 ◽  
Author(s):  
Xin Sui ◽  
Shijian Deng ◽  
Mengmeng Liu ◽  
Linlin Fan ◽  
Yunfei Wang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Bone Growth ◽  
Osteoclast Differentiation ◽  
Marker Genes ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bone Homeostasis ◽  
Micro Computed Tomography ◽  
Constitutive Activation

Background/Aims: Activation of the Wnt/β-catenin signalling pathway has been widely investigated in bone biology and shown to promote bone formation. However, its specific effects on osteoclast differentiation have not been fully elucidated. Our study aimed to identify the role of β-catenin in osteoclastogenesis and bone homeostasis. Methods: In the present study, exon 3 in the β-catenin gene (Ctnnb1) allele encoding phosphorylation target serine/threonine residues was flanked by floxP sequences. We generated mice exhibiting conditional β-catenin activation (Ctsk-Cre;Ctnnb1flox(exon3)/+, designated CA-β-catenin) by crossing Ctnnb1flox(exon3)/flox(exon3) mice with osteoclast-specific Ctsk-Cre mice. Bone growth and bone mass were analysed by micro-computed tomography (micro-CT) and histomorphometry. To further examine osteoclast activity, osteoclasts were induced from bone marrow monocytes (BMMs) isolated from CA-β-catenin and Control mice in vitro. Osteoclast differentiation was detected by tartrate-resistant acid phosphatase (TRAP) staining, immunofluorescence staining and reverse transcription-quantitative PCR (RT–qPCR) analysis. Results: Growth retardation and low bone mass were observed in CA-β-catenin mice. Compared to controls, CA-β-catenin mice had significantly reduced trabecular bone numbers under growth plates as well as thinner cortical bones. Moreover, increased TRAP-positive osteoclasts were observed on the surfaces of trabecular bones and cortical bones in the CA-β-catenin mice; consistent results were observed in vitro. In the CA-β-catenin group, excessive numbers of osteoclasts were induced from BMMs, accompanied by the increased expression of osteoclast-associated marker genes. Conclusion: These results indicated that the constitutive activation of β-catenin in osteoclasts promotes osteoclast formation, resulting in bone loss.

scholarly journals Forsythia suspensa Protects against Bone Loss in Ovariectomized Mice

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1831 ◽  
Author(s):  
Youn-Hwan Hwang ◽  
Seon-A Jang ◽  
Taesoo Kim ◽  
Hyunil Ha
Keyword(s):  
Bone Loss ◽  
Trabecular Bone ◽  
Osteoclast Differentiation ◽  
Water Extract ◽  
Nuclear Factor ◽  
Micro Computed Tomography ◽  
Activated T Cells ◽  
Beneficial Effects ◽  
Ovariectomized Mice ◽  
Forsythia Suspensa

In traditional oriental medicine, the fruit of Forsythia suspensa has been used as a nutritional supplement to alleviate inflammation and treat gastrointestinal diseases. However, there is no information available on its beneficial effects on bone. We investigated the beneficial effects of F. suspensa water extract (WFS) on osteoclast differentiation and bone loss. The microarchitecture of trabecular bone was analyzed by micro-computed tomography. Osteoclast differentiation was evaluated based on tartrate-resistant alkaline phosphatase activity, and bone resorption activity was examined on a bone-like mineral surface. The mechanism of action of WFS was assessed by evaluating the expression and activation of signaling molecules. Phytochemical constituents were identified and quantitated by ultrahigh-performance liquid chromatography–tandem mass spectrometry. WFS reduced ovariectomy-induced trabecular bone loss and inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and resorption activity. WFS suppressed RANKL-induced expression of nuclear factor of activated T cells cytoplasmic 1, a crucial transcription factor for osteoclast differentiation by decreasing c-Fos protein levels and suppressing the activation of p38 and c-Jun-N-terminal kinase. We also identified 12 phytochemicals in WFS including lignans, phenylethanoids, and flavonoids. Collectively, these results suggest that WFS inhibits osteoclast differentiation and can potentially be used to treat postmenopausal osteoporosis.

scholarly journals Chitosan oligosaccharide inhibits skull resorption induced by lipopolysaccharides in mice

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ke Guo ◽  
Zong Lin Liu ◽  
Wen Chao Wang ◽  
Wei Feng Xu ◽  
Shi Qi Yu ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Therapeutic Potential ◽  
Bone Destruction ◽  
Osteoclast Formation ◽  
Water Soluble ◽  
Tartrate Resistant Acid Phosphatase ◽  
Chitosan Oligosaccharide ◽  
Micro Computed Tomography ◽  
Bone Damage ◽  
Dose Dependent Decrease

Abstract Background Low-molecular-weight chitosan oligosaccharide (LMCOS), a chitosan degradation product, is water-soluble and easily absorbable, rendering it a popular biomaterial to study. However, its effect on bone remodelling remains unknown. Therefore, we evaluated the effect of LMCOS on lipopolysaccharide (LPS)-induced bone resorption in mice. Methods Six-week-old male C57BL/6 mice (n = five per group) were randomly divided into five groups: PBS, LPS, LPS + 0.005% LMCOS, LPS + 0.05% LMCOS, and LPS + 0.5% LMCOS. Then, the corresponding reagents (300 μL) were injected into the skull of the mice. To induce bone resorption, LPS was administered at 10 mg/kg per injection. The mice were injected three times a week with PBS alone or LPS without or with LMCOS and sacrificed 2 weeks later. The skull was removed for micro-computed tomography, haematoxylin-eosin staining, and tartrate-resistant acid phosphatase staining. The area of bone damage and osteoclast formation were evaluated and recorded. Results LMCOS treatment during LPS-induced skull resorption led to a notable reduction in the area of bone destruction; we observed a dose-dependent decrease in the area of bone destruction and number of osteoclasts with increasing LMCOS concentration. Conclusions Our findings showed that LMCOS could inhibit skull bone damage induced by LPS in mice, further research to investigate its therapeutic potential for treating osteolytic diseases is required.

scholarly journals Melatonin restores osteoporosis-impaired osteogenic potential of bone marrow mesenchymal stem cells and alleviates bone loss through the HGF/PTEN/Wnt/β-catenin axis

2021 ◽  
Vol 12 ◽  
pp. 204062232199568
Author(s):  
Jun Zhang ◽  
Guoliang Jia ◽  
Pan Xue ◽  
Zhengwei Li
Keyword(s):  
Bone Marrow ◽  
Bone Loss ◽  
Osteogenic Differentiation ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Osteogenic Potential ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tartrate Resistant Acid Phosphatase ◽  
Micro Computed Tomography ◽  
Alizarin Red

Background: Previous studies reported that melatonin exerts its effect on mesenchymal stem cell (MSC) survival and differentiation into osteogenic and adipogenic lineage. In the current study we aimed to explore the effect of melatonin on osteoporosis and relevant mechanisms. Methods: Real-time qualitative polymerase chain reaction (RT-qPCR) and Western blot analysis were conducted to determine expression of HGF, PTEN, and osteoblast differentiation-related genes in ovariectomy (OVX)-induced osteoporosis mice and the isolated bone marrow MSCs (BMSCs). Pre-conditioning with melatonin (1 μmol/l, 10 μmol/l and 100 μmol/l) was carried out in OVX mice BMSCs. Bone microstructure was analyzed using micro-computed tomography and the contents of alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase 5b (TRAP5b) were detected by enzyme-linked immunosorbent assay in serum. BMSC proliferation was measured by cell-counting kit (CCK)-8 assay. Alizarin red S (ARS) staining and ALP activity assay were performed to assess BMSC mineralization and calcification. The activity of the Wnt/β-catenin pathway was evaluated by dual-luciferase reporter assay. Results: Melatonin prevented bone loss in OVX mice. Melatonin increased ALP expression and reduced TRAP5b expression. HGF and β-catenin were downregulated, while PTEN was upregulated in the femur of OVX mice. Melatonin elevated HGF expression and then stimulated BMSC proliferation and osteogenic differentiation. Additionally, HGF diminished the expression of PTEN, resulting in activated Wnt/β-catenin pathway both in vitro and in vivo. Furthermore, melatonin was shown to ameliorate osteoporosis in OVX mice via the HGF/ PTEN/ Wnt/β-catenin axis. Conclusion: Melatonin could potentially enhance osteogenic differentiation of BMSCs and retard bone loss through the HGF/ PTEN/ Wnt/β-catenin axis.

scholarly journals Scopolin Attenuates Osteoporotic Bone Loss in Ovariectomized Mice

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3565
Author(s):  
Eunkuk Park ◽  
Jeonghyun Kim ◽  
Hyun-Seok Jin ◽  
Chun Whan Choi ◽  
Tae Hyun Choi ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Bone Destruction ◽  
Osteoporotic Bone ◽  
Nodule Formation ◽  
Mineral Density ◽  
Bone Mineral Density Loss ◽  
Treatment And Prevention ◽  
Ovariectomized Mice ◽  
Bioactive Constituent

Bone remodeling is a renewal process regulated by bone synthesis (osteoblasts) and bone destruction (osteoclasts). A previous study demonstrated that Lycii radicis cortex (LRC) extract inhibited ovariectomized (OVX)-induced bone loss in mice. This study investigated the anti-osteoporotic effects of bioactive constituent(s) from the LRC extract. The effective compound(s) were screened, and a single compound, scopolin, which acts as a phytoalexin, was chosen as a candidate component. Scopolin treatment enhanced alkaline phosphatase activity and increased mineralized nodule formation in MC3T3-E1 pre-osteoblastic cells. However, osteoclast differentiation in primary-cultured monocytes was reduced by treatment with scopolin. Consistently, scopolin treatment increased osteoblast differentiation in the co-culture of monocytes (osteoclasts) and MC3T3-E1 (osteoblast) cells. Scopolin treatment prevented bone mineral density loss in OVX-induced osteoporotic mice. These results suggest that scopolin could be a therapeutic bioactive constituent for the treatment and prevention of osteoporosis.

scholarly journals Rapamycin Alleviates Cancellous Bone Loss and Cortical Bone Porosity in Ovariectomized Mice but Not Overall Biomechanical Performance

2021 ◽  
Author(s):  
Ruoyao Li ◽  
Junhao Liu ◽  
Zhiping Huang ◽  
Xiuhua Wu ◽  
Zhou Yang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Cortical Bone ◽  
Cancellous Bone ◽  
Sham Group ◽  
Biomechanical Properties ◽  
Bending Test ◽  
Tartrate Resistant Acid Phosphatase ◽  
Long Bones ◽  
Ovariectomized Mice ◽  
Vascular Canal

Abstract Background: Recent studies have shown that rapamycin (Rapa) rescues cancellous bone loss of osteoporosis models, but its effects on cortical bone and the biomechanical properties remain uncertain. This study was aimed to determine whether rapamycin improve the quality of long bones in ovariectomy (OVX)-induced osteoporosis.Methods: Thirty female C57BL/6J mice were randomly divided into Sham, OVX and OVX+Rapa group. Mice in the OVX+Rapa group were injected intraperitoneally with 1.5 mg/kg rapamycin daily after ovariectomy. After 12 weeks, the microstructures of femurs and the vascular canal porosity tibiae were analyzed by micro-CT. The compressive stiffness of the distal femurs was calculated with the micro-finite element method, and the bending strength of the tibiae was evaluated with a three-point bending test. Western blot of LC3, P62 was used to assess autophagy activity of bone. The number of osteoclasts was quantified by tartrate-resistant acid phosphatase (TRAP) staining. ELISA detected the concentration of bone-specific alkaline phosphatase (BALP) in serum.Results: OVX led to a decrease in cross-sectional areas of the mid-diaphyses and distal femoral cortical bones, increasing the cortical bone vascular canal porosity from 1.42% to 4.79%. The rapamycin reduced cancellous bone loss and decreased cortical bone vascular canal porosity by 3.9%, but further reduced the thickness of the distal femoral cortical bone by 16.7%, with no significant effect on the cortical bone in the mid-diaphyses. Compared to the Sham group, OVX mice showed a decrease in distal femoral stiffness to 6497 N/mm and a decrease in tibial maximum load to 6.08 N, while rapamycin intervention did not significantly improve the decreased biomechanical properties. Moreover, rapamycin remarkably reduced the TRAP-positive osteoclasts and the concentration of serum BALP by 80.6% and 30.8%, respectively. Autophagy was activated in the OVX group compared with the sham group.Conclusions: This study has demonstrated that rapamycin ameliorates cancellous bone loss and cortical bone porosity in ovariectomized mice but partly reduces the size of cortical bone, while has no effect on improving the biomechanical performance. Additionally, the present study also proved that OVX led to both cancellous and cortical bone loss, with attenuated biomechanical properties of long bones.

scholarly journals The Ginsenoside Exhibits Antiosteoporosis Effects in Ketogenic-Diet-Induced Osteoporosis via Rebalancing Bone Turnover

2021 ◽  
Vol 11 ◽  
Author(s):  
Qi Liu ◽  
Jian Zhou ◽  
Zhou Yang ◽  
Chuhai Xie ◽  
Yan Huang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Ketogenic Diet ◽  
Cancellous Bone ◽  
Volume Fraction ◽  
Cathepsin K ◽  
Tartrate Resistant Acid Phosphatase ◽  
Protective Effects ◽  
Bone Volume Fraction ◽  
Ppar Γ ◽  
Ginsenoside Rb2

Ginsenoside is widely used in China for therapeutic and healthcare practice. Ginsenoside-Rb2 shows the antiosteoporosis effects in ovariectomized rodents. However, the protective effects on osteoporosis induced by ketogenic diet (KD) remain unknown. Therefore, this study aimed at evaluating the effects of ginsenoside-Rb2 on KD-induced osteoporosis. Thirty mice were randomly divided into three groups: sham, KD, and KD + Rb2. Bone microstructures, biomechanical properties, concentrations of serum bone alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase (TRACP), and protein expression of osteocalcin (OCN), peroxisome proliferation-activated receptor γ (PPAR-γ), cathepsin K, and TRAP were evaluated after a 12-week intervention. The results show that KD induced significant bone loss and biomechanical impairment. Ginsenoside-Rb2 attenuated significant bone loss and maintained biomechanics in cancellous bone. The bone volume fraction increased from 2.3 to 6.0% in the KD + Rb2 group than that in the KD group. Meanwhile, ginsenoside-Rb2 effectively maintained biomechanical strengths in cancellous bone, increased serum BALP and decreased TRACP, and upregulated OCN and downregulated TRAP, PPAR-γ, and cathepsin K in the KD mice. This study demonstrated that ginsenoside-Rb2 retards bone loss and maintains biomechanics with KD. The underlying mechanism might be that ginsenoside-Rb2 inhibits bone resorption process and induces osteogenic differentiation, providing evidence for ginsenoside as being an alternative option for osteoporosis induced by KD.

scholarly journals Erythrina variegata extract exerts osteoprotective effects by suppression of the process of bone resorption

2010 ◽  
Vol 104 (7) ◽  
pp. 965-971 ◽  
Author(s):  
Yan Zhang ◽  
Qi Li ◽  
Xiaoli Li ◽  
Hoi-Ying Wan ◽  
Man-Sau Wong
Keyword(s):  
Bone Resorption ◽  
Osteoclast Differentiation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Sham Operation ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Erythrina Variegata ◽  
Bone Properties ◽  
Ovariectomised Rats

Our previous study showed that Erythrina variegata L. (EV) inhibited bone loss and improved bone properties in ovariectomised rats. The purpose of the present study is to investigate the potential mechanism involved in mediating the osteoprotective actions of EV. Female Sprague–Dawley rats were fed a phyto-oestrogen-free diet and subjected to either ovariectomy or a sham operation. Ovariectomised rats were treated with genistein (40 mg/kg) as well as low (200 mg/kg), medium (500 mg/kg) or high (1000 mg/kg) doses of EV extract. Bone properties and mRNA expressions were evaluated by micro-computed tomography and quantitative RT-PCR, respectively. Osteoclast differentiation in RAW 264·7 cells was studied by tartrate-resistant acid phosphatase (TRAP) staining. High doses of EV could decrease urinary Ca and P excretion, maintain serum Ca and P level, and exert beneficial effects on the micro-structure and morphology of trabecular bone and cortical bone in ovariectomised rats. EV suppressed the up-regulation of cathepsin K mRNA and the down-regulation of osteoprotegrin mRNA in the tibia of ovariectomised rats. TRAP-positive cell numbers were significantly decreased in receptor activator of nuclear factor-κB ligand (RANKL)-induced RAW 264·7 cells when co-cultured with EV extracts. The present study indicated that the protective effects of EV on bone properties in ovariectomised rats are likely to be mediated by its inhibitory actions on the process of bone resorption via the suppression of osteoclast differentiation and maturation.

scholarly journals Effects of Jixueteng on Experimental Periodontitis During Orthodontic Tooth Movement in Rats

2021 ◽  
Vol 16 (4) ◽  
pp. 1934578X2110024
Author(s):  
Taira Katayama ◽  
Takenori Sato ◽  
Nobushiro Hamada ◽  
Seiji Goda ◽  
Tetsutaro Yamaguchi ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Orthodontic Treatment ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Bone Destruction ◽  
Infected Group ◽  
Tartrate Resistant Acid Phosphatase ◽  
Micro Computed Tomography ◽  
Experimental Periodontitis

Recently, natural ingredients have focused on the inhibition of bacteria-induced alveolar bone resorption in orthodontic treatment. Jixueteng (Jix), a Chinese traditional medicine, contains several kinds of flavonoids given their biological properties. We evaluated the effects of Jix on experimental periodontitis during orthodontic tooth movement (OTM) in rats. To this end, 9-week-old male Wistar rats, which were equipped with orthodontic appliance, were orally infected with Porphyromonas gingivalis (Pg), while Jix was administered in their drinking water. A total of 28 days after the beginning of OTM, alveolar bone resorption on the right side of the upper jaws was scanned with micro-computed tomography. These were also used as histological specimens and underwent tartrate-resistant acid phosphatase (TRAP) staining. TRAP-positive multinucleated cells were counted as osteoclasts. As a result, the distance of tooth movement in the OTM and Pg infection with Jix administration (OTM + Pg + Jix) group was the same as that of the sham-infected group. The amount of bone resorption and number of osteoclasts in the OTM + Pg + Jix group was more significantly decreased than that in the OTM and Pg-infected group ( P < 0.05). Hence, Jix had little effect on OTM and inhibited Pg-induced alveolar bone destruction. We suggested that the administration of Jix can support tooth movement and contribute to the prevention of periodontitis during orthodontic treatment.

scholarly journals Effects of Hot Water Extracts fromPolygonum multiflorumon Ovariectomy Induced Osteopenia in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yun-Ho Hwang ◽  
Kyung-Yun Kang ◽  
Jong-Jin Kim ◽  
Sung-Ju Lee ◽  
Young-Jin Son ◽  
...  
Keyword(s):  
Bone Loss ◽  
Group Treatment ◽  
Histological Analysis ◽  
Bone Alkaline Phosphatase ◽  
Hot Water ◽  
Tartrate Resistant Acid Phosphatase ◽  
Polygonum Multiflorum ◽  
Oral Gavage ◽  
Nonalcoholic Fatty Liver ◽  
Hematoxylin And Eosin

Polygonum multiflorum(PM), a traditional Chinese medicine, is used to treat various diseases including nonalcoholic fatty liver disease and hyperlipidemia. However, the influence of PM on osteoporosis in animals is unclear. The present study investigated the antiosteoporotic effect of PM on bone mass in ovariectomized (OVX) mice and its possible mechanism of action. Twenty-five female C3H/HeN mice were divided into five groups of five mice as follows. Sham-operated control mice received daily oral gavage of an equal volume of water, and OVX mice received daily oral gavage of water or an injection ofβ-estradiol or PM for 6 weeks. Administration of PM significantly suppressed body weight and organs weight and increased weight and length of bone compared with the OVX group. Treatment with PM reversed osteopenia in OVX mice, thereby improving the bone morphometric parameters. Moreover, histological analysis using hematoxylin and eosin staining showed that PM inhibited OVX-induced bone loss. Serum estradiol and bone alkaline phosphatase levels were significantly decreased in the OVX group, with the levels increasing with PM treatment. In addition, tartrate-resistant acid phosphatase activity was inhibited by PM in OVX mice. These results suggest that PM is effective in preventing bone loss in OVX mice.

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