Cell‐free culture supernatant of Lactobacillus curvatus Wikim38 inhibits RANKL‐induced osteoclast differentiation and ameliorates bone loss in ovariectomized mice

2021 ◽  
Author(s):  
Ah‐Ra Jang ◽  
Joon‐Suk Park ◽  
Dong‐Kyu Kim ◽  
Ji‐Yeon Park ◽  
Jae‐Hun Ahn ◽  
...  
Keyword(s):  
Bone Loss ◽  
Culture Supernatant ◽  
Osteoclast Differentiation ◽  
Lactobacillus Curvatus ◽  
Ovariectomized Mice ◽  
Cell Free Culture Supernatant

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.

Identification and Functional Characterization of Metabolites for Bone Mass in Peri-/Post-menopausal Chinese Women

2021 ◽  
Author(s):  
Rui Gong ◽  
Hong-Mei Xiao ◽  
Yin-Hua Zhang ◽  
Qi Zhao ◽  
Kuan-Jui Su ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Dodecanoic Acid ◽  
Mineral Density ◽  
Ovariectomized Mice ◽  
Post Menopausal ◽  
Functional Mechanisms

Abstract Context Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. Objective We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri-/post-menopausal women. Design and Methods We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares (PLS) regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. Results Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module, causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. DA treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (e.g.,10, 100μM). Conclusions This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.

scholarly journals Water Extract of Lysimachia christinae Inhibits Trabecular Bone Loss and Fat Accumulation in Ovariectomized Mice

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1927
Author(s):  
Ki-Shuk Shim ◽  
Youn-Hwan Hwang ◽  
Seon-A Jang ◽  
Taesoo Kim ◽  
Hyunil Ha
Keyword(s):  
Bone Loss ◽  
Trabecular Bone ◽  
Body Weight Gain ◽  
Osteoclast Differentiation ◽  
Water Extract ◽  
Mitogen Activated Protein Kinase ◽  
Nuclear Factor ◽  
Fat Accumulation ◽  
Ovariectomized Mice ◽  
Trabecular Bone Loss

In Asia, extracts of Lysimachia christinae have been used for liver or urinogenital system-related diseases in traditional medicine. In this study, we investigated the effects of the water extract of L. christinae (WELC) on receptor activator of nuclear factor-kappa Β ligand (RANKL)-induced osteoclastic differentiation of bone marrow macrophages, and on osteoporosis and obesity in ovariectomy mice. RANK signaling pathways related to osteoclast differentiation were examined by real-time polymerase chain reaction (PCR) and western blot analysis. Additionally, we performed micro-computed tomography to assess trabecular bone loss, histological analysis for fat accumulation in adipose, liver, and bone tissues, and phytochemical profiling for WELC characterization. WELC significantly inhibited osteoclast differentiation by downregulating RANKL-induced mitogen-activated protein kinase (MAPK)/c-Fos/nuclear factor of activated T-cells (NFAT) signaling in osteoclast precursors and ovariectomy-induced trabecular loss by suppressing osteolcastic bone resorption. WELC markedly decreased ovariectomy-induced body weight gain and fat accumulation in adipose, liver, and bone tissues. Furthermore, ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) identified 16 phytochemicals in WELC when compared with the mass fragmentation of standard chemicals. Collectively, these results suggest that WELC might possess beneficial effects on postmenopausal osteoporosis by inhibiting osteoclast differentiation and obesity by suppressing fat accumulation.

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 Circaea Mollis Siebold & Zucc. Prevents Bone Loss in a Mouse Postmenopausal Osteoporosis Model by Promoting of Osteoblast Differentiation (P06-130-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Gyhye Yoo ◽  
Ji-Hye Park ◽  
Yang-Ju Son ◽  
Chang Ho Lee ◽  
Chu Won Nho
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Bone Loss ◽  
Postmenopausal Osteoporosis ◽  
Osteoclast Differentiation ◽  
Mineral Density ◽  
Promising Alternative ◽  
Ovariectomized Mice

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

scholarly journals Anti-Osteoporotic Effects of Combined Extract of Lycii Radicis Cortex and Achyranthes japonica in Osteoblast and Osteoclast Cells and Ovariectomized Mice

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2716 ◽  
Author(s):  
Eunkuk Park ◽  
Jeonghyun Kim ◽  
Subin Yeo ◽  
Eunguk Lim ◽  
Chun Whan Choi ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Osteoporotic Bone ◽  
Osteoblastic Cell ◽  
Mouse Bone Marrow ◽  
Osteoblastic Cell Line ◽  
Ovariectomized Mice ◽  
Achyranthes Japonica

Osteoporosis is characterized by low bone density and quality with high risk of bone fracture. Here, we investigated anti-osteoporotic effects of natural plants (Lycii Radicis Cortex (LRC) and Achyranthes japonica (AJ)) in osteoblast and osteoclast cells in vitro and ovariectomized mice in vivo. Combined LRC and AJ enhanced osteoblast differentiation and mineralized bone-forming osteoblasts by the up-regulation of bone metabolic markers (Alpl, Runx2 and Bglap) in the osteoblastic cell line MC3T3-E1. However, LRC and AJ inhibited osteoclast differentiation of monocytes isolated from mouse bone marrow. In vivo experiments showed that treatment of LRC+AJ extract prevented OVX-induced trabecular bone loss and osteoclastogenesis in an osteoporotic animal model. These results suggest that LRC+AJ extract may be a good therapeutic agent for the treatment and prevention of osteoporotic bone loss.

Safflower bud inhibits RANKL-induced osteoclast differentiation and prevents bone loss in ovariectomized mice

Phytomedicine ◽  
2017 ◽  
Vol 34 ◽  
pp. 6-13 ◽  
Author(s):  
Joo-Hee Choi ◽  
Seul-Ki Lim ◽  
Dong-Il Kim ◽  
Min-Jung Park ◽  
Young-Kuk Kim ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Ovariectomized Mice

scholarly journals Antiosteoporosis Activity of New Oriental Medicine Preparation (Kyungokgo Mixed with Water Extract ofHovenia dulcis) on the Ovariectomized Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Yun-Ho Hwang ◽  
Kwang-Jin Kim ◽  
Jong-Jin Kim ◽  
Kyung-Yun Kang ◽  
Sung-Ju Lee ◽  
...  
Keyword(s):  
Bone Loss ◽  
Cell Population ◽  
Immune Cell ◽  
Osteoclast Differentiation ◽  
Water Extract ◽  
Oriental Medicine ◽  
Trabecular Microarchitecture ◽  
Immune Cell Population ◽  
Ovariectomized Mice ◽  
Hovenia Dulcis

Protective effect of new oriental medicine (Kyungokgo mixed with water extract ofHovenia dulcis, KOGHD) was assessed on the bone loss induced mice by ovariectomy. In thein vivoexperiments, antiosteoporosis effect of KOGHD was investigated using ovariectomized osteoporosis mice model. After 6 weeks of treatment, the mice were euthanized, and the effect of Kyungokgo (KOG) and KOGHD on body weight, spleen weigh, thymus weight, uterine weight, serum biochemical indicators, bone weight and length, immune cell population, bone morphometric parameters, and histological stains was observed. Our results showed that KOGHD prevented the deterioration of trabecular microarchitecture caused by ovariectomy, which were accompanied by the lower levels of bone turnover markers and immune cell population as evidenced by the inhibition of RANKL-mediated osteoclast differentiation without cytotoxic effect on bone marrow derived macrophages (BMMs). Therefore, these results suggest that theHovenia dulcis(HD) supplementation in the KOG may also prevent and treat bone loss.

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