MACROMOLECULAR RAPID COMMUNICATIONS
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2013
·Vol. 35
·期 5
·574-578
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IF 4.929
Jingwen Liao,Haobo Pan,Chengyun Ning,Guoxin Tan,Zhengnan Zhou,Junqi Chen,Shishu Huang
In this article, taurine, one of the small biomolecules associated with bone metabolism, is firstly utilized to induce the fabrication of nano-architectured conducting polypyrrole (NCPPy) on biomedical titanium in diverse pH values of phosphate buffer solution (PBS). Accordingly, the possible mechanism for the fabrication of NCPPy is proposed, which is dependent on the states of polytaurine from the polymerization of taurine, i.e., the inability of forming polytaurine and unordered restricted space results in taurine-incorporated and polytaurine-incorporated tightly packed nanoparticles (pH 6.2 and 8.0), respectively, and however, ordered restricted space constructed by polytaurine chains induces the fabrication of polytaurine-incorporated nanopillars (pH 6.8) and polytaurine-incorporated nanowire networks (pH 7.4).
研究领域:
生物医学工程
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材料科学
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骨科
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL FOOD
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2016
·Vol. 19
·期 1
·1-14
·
IF 1.844
Xi Zheng,Sun-Kyeong Lee,Ock K. Chun
Osteoporosis is an age-related disorder that affects both women and men, although estrogen deficiency induced by menopause accelerates bone loss in older women. As the demographic shifts to a more aged population, a growing number of men and women will be afflicted with osteoporosis. Since the current drug therapies available have multiple side effects, including increased risk of developing certain types of cancer or complications, a search for potential nonpharmacologic alternative therapies for osteoporosis is of prime interest. Soy isoflavones (SI) have demonstrated potential bone-specific effects in a number of studies. This article provides a systematic review of studies on osteoporotic bone loss in relation to SI intake from diet or supplements to comprehensively explain how SI affect the modulation of bone remodeling. Evidence from epidemiologic studies supports that dietary SI attenuate menopause-induced osteoporotic bone loss by decreasing bone resorption and stimulating bone formation. Other studies have also illustrated that bone site-specific trophic and synergistic effects combined with exercise intervention might contribute to improve the bioavailability of SI or strengthen the bone-specific effects. To date, however, the effects of dietary SI on osteoporotic bone loss remain inconclusive, and study results vary from study to study. The current review will discuss the potential factors that result in the conflicting outcomes of these studies, including dosages, intervention materials, study duration, race, and genetic differences. Further well-designed studies are needed to fully understand the underlying mechanism and evaluate the effects of SI on osteoporosis in humans.
研究领域:
营养学
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内分泌学
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骨骼健康
✓ 已验证
DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2025
·
IF 5.1
Xuehui Deng,Bingfeng Lin,Wenlong Xiao,Fang Wang,Pingcui Xu,Nani Wang
Background Specnuezhenide (SPN) is an iridoid glycoside isolated from Fructus Ligustri Lucidi, an herb prescribed for the treatment of senile osteoporosis. However, the direct role of SPN on bone metabolism remains unclear. In this study, the effects of SPN on d-galactose (d-gal)-induced mice, bone marrow mesenchymal stem cells (BMSCs), and nuclear factor-κB ligand-induced osteoclasts were examined.Methods Micro-computed tomography was used to observe the bone microstructure. Osteogenesis was examined using Western blotting and alkaline phosphatase staining. Osteoclastogenesis was examined using Western blotting and F-actin ring staining. Senescence-associated β-galactosidase was used to detect cell senescence. In addition, the expression of Takeda G protein-coupled receptor 5 (TGR5)/farnesoid X receptor (FXR) signaling pathway-related genes and proteins was determined through quantitative real-time polymerase chain reaction and immunofluorescence.Results Oral administration of SPN improved the bone microstructure in d-gal-induced mice and increased bone mineral density, bone volume, trabecular thickness, and trabecular number. SPN also upregulated the expression of the osteogenesis markers osteocalcin, bone morphogenetic protein 2, and runt-related transcription factor 2 and downregulated the expression of the osteoclasis markers tartrate-resistant acid phosphatase, nuclear factor-κB, and nuclear factor of activated T-cells in the d-gal-induced bone. Furthermore, SPN increased alkaline phosphatase staining, inhibited F-actin ring formation, and reduced the activity of senescence-associated β-galactosidase in vitro. Mechanistically, SPN activated the TGR5/FXR pathway in d-gal-induced BMSCs and osteoclasts. The protective effects of SPN were abolished after addition of the TGR5 inhibitor SBI-115 or FXR inhibitor DY268. Moreover, SPN could elevate the protein and mRNA levels of TGR5, FXR, and the downstream small heterodimer partner in d-gal-induced bone.Conclusion SPN alleviated senile osteoporosis and cell senescence by activating the TGR5/FXR pathway.
研究领域:
药理学
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骨生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Huanhuan Xu,Titi Liu,Lihong Hu,Jin Li,Chunxia Gan,Jing Xu,Fei Chen,Zemin Xiang,Xuanjun Wang,Jun Sheng
Caffeine (1,3,7-trimethylxanthine) is a naturally occurring plant xanthine alkaloid present in many commonly consumed beverages worldwide, including tea, coffee, and cocoa. Although moderate caffeine intake is generally considered to exert positive effects on human health, its effect on bone metabolism remains controversial. The aim of this study was to systematically evaluate the pharmacological effect of long-term administration of caffeine on ovariectomy-induced postmenopausal osteoporosis in female rats. A sham operation or ovariectomy was performed to establish the ovariectomy rat model. The ovariectomized (OVX) rats were divided into five subgroups: OVX with vehicle (model), OVX with raloxifene hydrochloride (RLX, positive control; 4 mg/kg body weight/day), and OVX with low-, medium-, and high-dose caffeine (9.6, 19.2, and 38.4 mg/kg of body weight/day, respectively). Their corresponding treatments were administered intragastrically for 13 weeks. In-vivo studies showed that treatment with caffeine effectively improved the lipid profiles and increased the concentration of calcium in the serum of OVX rats. Medium- or high-dose treatment with caffeine significantly decreased the activities of alkaline and acid phosphatases in OVX rats. In addition, treatment with caffeine (at any dose) did not adversely affect organ weights, organ coefficients, femoral length, bone mineral density, biomechanical properties, or bone microarchitecture in OVX rats. Collectively, our study demonstrated that caffeine did not exert a damaging effect on the skeletal system of OVX rats.
研究领域:
药理学
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骨骼健康
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动物模型
✓ 已验证
DOI
PubMed
高影响因子
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
·
2016
·Vol. 18
·期 31
·21789-21796
·
IF 4.449
Ming Wang,Liping Wang,Chao Shi,Tian Sun,Yi Zeng,Yingchun Zhu
Aluminum (Al) is a trace element found in hard tissues, and the induction of bone diseases by Al accumulation has generated interest in the role and mechanism of Al in bone metabolism. Because hydroxyapatite (HA) constitutes the main inorganic content of human hard tissues, the biological effect of Al in human hard tissues is closely related to the intrinsic state of Al-doped HA (Al-HA). However, few investigations to date have focused on the crystallography of Al-HA. Herein, we determined the crystallographic characteristics and energy states of Al-HA by conducting theoretical and experimental studies. Al-HA [Ca10−1.5xAlx(PO4)6(OH)2] with a defect structure was synthesized. XRD patterns and morphology images revealed that doping of Al decreased the crystallinity and the HA nanocrystal size. The optimized crystal structure indicated that Al was preferentially substituted for Ca(2) and Ca vacancies appeared at the Ca(2)1 site. Al doping locally distorted the regularity and integrity of the HA crystal structure, leading to the occurrence of Ca2+ vacancies and the displacement and rotation of OH− and [PO4]3− chains. The total energy of Al-HA increased and the stability decreased. Consequently, Al-HA might be readily degraded by osteoclasts and bone resorption could be accelerated. The destruction and over-resorption of bones caused by excessive Al could result in abnormal bone metabolism. The present findings not only provide the first crystallographic information on the disruptive effects of Al doping in HA but also complement the present understanding of the mechanisms underlying Al-induced bone diseases.
研究领域:
材料科学
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生物医学
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计算化学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2018
·Vol. 9
·期 4
·2251-2260
·
IF 3.289
Guo Liu,Shengwei Sun,Baoyan Guo,Benchun Miao,Zhen Luo,Zumeng Xia,Danyang Ying,Fei Liu,Bin Guo,Jian Tang,Yong Cao,Jianyin Miao
Casein phosphopeptides (CPPs) have been demonstrated to be calcium chelators. Unfortunately, few studies have been reported on the effects of CPPs on the mechanism of the uptake and absorption of Ca2+ and bone metabolism. In this study, a monomeric peptide fraction isolated by RP-HPLC (F6-1) that possessed high calcium transport capacity in Caco-2 cell monolayers was separated and characterized. The effects of F6-1 on the absorption mechanisms of Ca2+ in a Caco-2 monolayer model and bone metabolism in rats were investigated. F6-1 was isolated by preparative and analytical RP-HPLC. Results for calcium transport suggested that the rates of Ca2+ transportation by F6-1 were approximately 2.57, 2.87 and 2.38 times higher than those in the control group at 30, 60 and 120 min, respectively. Results of ultraviolet (UV) spectroscopy indicated that the intensity of UV absorption changed because of the binding of Ca2+ to F6-1. Analysis of transepithelial electrical resistance (TEER) and the expression of TRPV6 in Caco-2 cells showed that F6-1 was likely to influence the transcellular pathway of intestinal absorption of Ca2+ rather than the paracellular pathway. Furthermore, the F6-1 group (1% Ca, 0.03% F6-1) exhibited increases in serum Ca2+ levels, femur length and femur Ca and decreases in serum alkaline phosphatase (ALP) levels and urinary pyridinoline content in a Sprague-Dawley rat model, which implied that F6-1 was beneficial for bone calcification. Overall, our results suggested that F6-1 enhanced the transport of Ca2+ in Caco-2 cells by affecting the transcellular pathway by upregulating the expression of TRPV6. F6-1 also improved bone formation and prevented bone resorption to benefit bone health in rats, which provided a basis for using F6-1 in calcium supplements or functional foods.
研究领域:
营养学
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生物化学
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食品科学
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生理学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF HISTOCHEMISTRY
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2023
·
IF 2
Jing Guo,Chang-Yong Tong,Jian-Guang Shi,Xin-Jian Li,Xue-Qin Chen
Lung cancer is prone to bone metastasis, and osteopontin (OPN) has an important significance in maintaining bone homeostasis. The goal of this study was to explore the impact of OPN level on bone metabolism and the molecular mechanism of inhibiting bone metastasis in non-small cell lung cancer (NSCLC). The expression of OPN in NSCLC was ascertained by Western blot and immunohistochemistry, and the correlation between the expression level of OPN and survival of patients was analyzed. Then the shRNA technology was applied to reduce the expression of OPN in NSCLC cells, and CCK-8 assay was carried out to investigate the effect of low expression of OPN on the proliferation of NSCLC cells. In addition, the effects of low expression of OPN on osteoclast differentiation, osteoblast generation and mineralization were studied using osteoclast precursor RAW264.7 and human osteoblast SaOS-2 cells, and whether OPN could regulate miR-34c/ Notch pathway to affect bone metabolism was further explored. The findings showed that the high level of OPN in NSCLC was closely related to the poor prognosis of patients and the abnormal proliferation of NSCLC cell lines. The suppression of OPN was beneficial to inhibit the differentiation of osteoclasts and promote the mineralization of osteoblasts. Besides, this study confirmed that the deletion of OPN can regulate bone metabolism through the regulation of miR-34c/Notch1 pathway, which will contribute to inhibiting the occurrence of osteolytic bone metastasis in NSCLC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Jun Jiang,Baixiu Zhao,Jianpeng Xiao,Liang Shi,Wei Shang,Ye Shu,Zhiming Zhao,Junyi Shen,Jingjuan Xu,Hui Cai
Background Clinical studies indicated that postmenopausal osteoporosis (PMOP) often accompanied by iron overload risk factor, which exacerbated bone metabolism disorders and accelerated PMOP. Previous research found that multicomponent in Ligustri Lucidi Fructus (FLL) or wine-steamed FLL (WFLL) acted on the common targets of iron overload and PMOP simultaneously, which indicated that FLL and WFLL probably regulated iron/bone metabolism dually. Additionally, WFLL had more superior effect according to the theory of Chinese medicine for thousands of years. Purpose To reveal the “superior multi-component structure (SMCS)” and its molecular mechanisms in parallelly down-regulating iron overload and rescuing bone metabolism by WFLL. Designs and methods HPLC fingerprinting was established to compare the chemical profiles of FLL and WFLL; Then, the chemical compositions and quality markers of FLL and WFLL were analyzed by UPLC-Orbitrap-MS/MS coupled with OPLS-DA; The dynamic contents of quality markers and the multi-component structure at different wine steaming times (WST) were simultaneously determined by HPLC-DAD; Meanwhile, the dynamic efficacy of FLL at different WST were hunt by systematic zebrafish model. Subsequently, potential mechanism of WFLL in treating PMOP accompanied with iron overload was obtained from network pharmacology (NP) and molecular docking (MD). Finally, zebrafish and ovariectomy rat model were carried out to validate this potential mechanism. Results HPLC fingerprints similarity of 15 batches in FLL and WFLL were among 0.9-1.0. 126 compositions were identified, including 58 iridoids, 25 terpenes, 30 phenylethanoids, 7 flavonoids and 6 others. 20 quality markers associated with WFLL was revealed, and the ratio of Phenylethanols: Iridoids: Triterpenes (P/I/T) was converted from 1: 15: 4.5 to 1: 0.8: 0.9 during steaming (0 - 24 h) calculated by the quantification of 11 quality markers; The bone mineralization and motor performance of zebrafish larvae indicated that the optimum efficacy of WFLL at 12 h ( P < 0.05) in which the SMCS of P/I/T was converted to 1: 4: 1.8. NP discovered that BMP-Smad pathway is one of the potential mechanisms of FLL in anti PMOP and then regulated bone formation and iron overload simultaneously. MD revealed that 17 active ingredients and 10 core targets genes could spontaneously bind with appropriate affinity. Rats model verified that FLL and WFLL significantly reversed PMOP, based on the improvement in bone formation indexes (ALP, OPG, OGN), iron metabolism indicators (hepcidin, ferritin), bone microstructure (BMD, BV/TV, Tb. Th, Tb. N); Moreover, WFLL significant enhanced reversal effect in anti-PMOP compared to FLL ( P < 0.05). FLL and WFLL increased genes and proteins expression (Hep, BMP-6, p-Smad1/5, Smad4) related to BMP-Smad pathway compared with model group, and WFLL was more superior than FLL ( P < 0.05). Conclusion The SMCS of FLL was optimized by wine-steam, WFLL represented a dual effect in downregulating iron overload and promoting bone formation, and the BMP-Smad pathway is one of the potential molecular mechanisms.
研究领域:
药理学
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中药学
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骨代谢
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铁代谢
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网络药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Natural Product Communications
·
2024
·
IF 1.5
Jing Wang,Yuqian Yang,Wenxin Wei,Xingyu Li,Feng Liu,Jianshu Liu,Wei Lan,Feng Gao,Hong Wang,Peifeng Wei
Background: Osteoporosis has emerged as a significant global public health concern, predominantly affecting postmenopausal women. Its pathogenesis is intricate and the disease course is protracted, imposing substantial medical burden on both society and individuals. Objective: To investigate the effects of 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glucoside (TSG) and acetylated-TSG (Ac-TSG) on osteoblast viability, in vivo pharmacokinetics in rats and anti-osteoporotic effects in ovariectomized rat model. Methods: Ac-TSG was obtained by acetylation of TSG, and the purity and structure of Ac-TSG were determined by HPLC and 1H NMR. The effects of TSG and Ac-TSG on MC3T3-E1 cell viability, pharmacokinetics in rats, blood biochemical indexes of OVX model rats were detected. Hematoxylin–eosin (HE) staining was used to observe bone tissue morphology, tartrate-resistant acid phosphatase (TRAP) staining was used to observe osteoclast morphology, micro-CT was used to perform three-dimensional reconstruction of femur, and femur parameters were analyzed. Results: The structure of the compound is Ac-TSG and the purity is more than 98%. Both TSG and Ac-TSG could reduce the damage of oxidative stress to MC3T3-E1 cells and effectively improve the levels of Ca, P, ALP and BGP in serum of OVX rats. Compared with TSG, Ac-TSG has a longer action time in vivo and can improve the femoral structure, the number of trabecular bone and the number of osteoclasts in rats. Conclusion: Ac-TSG conferred protection to MC3T3-E1 cells against oxidative stress-induced damage and enhanced their bioavailability. Simultaneously, Ac-TSG ameliorated abnormal bone metabolism and mitigated bone microstructural changes in OVX rats, exhibiting a protective effect against osteoporosis.
研究领域:
药理学
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骨科
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分子生物学
✓ 已验证
DOI
高影响因子
CELL PROLIFERATION
·
2020
·Vol. 54
·期 1
·e12955
·
IF 5.753
Jun Ma,Lei Zhu,Zhibin Zhou,Tengfei Song,Lei Yang,Xu Yan,Aimin chen,Tian Wen Ye
Objectives Calcium ion signals are important for osteoclast differentiation. Transient receptor potential vanilloid 6 (TRPV6) is a regulator of bone homeostasis. However, it was unclear whether TRPV6 was involved in osteoclast formation. Therefore, the aim of this study was to evaluate the role of TPRV6 in bone metabolism and to clarify its regulatory role in osteoclasts at the cellular level. Materials and methods Bone structure and histological changes in Trpv6 knockout mice were examined using micro-computed tomography and histological analyses. To investigate the effects of Trpv6 on osteoclast function, we silenced or overexpressed Trpv6 in osteoclasts via lentivirus transfection, respectively. Osteoclast differentiation and bone resorption viability were measured by tartrate-resistant acid phosphatase (TRAP) staining and pit formation assays. The expression of osteoclast marker genes, including cathepsin k, DC-STAMP, Atp6v0d2 and TRAP, was measured by qRT-PCR. Cell immunofluorescence and Western blotting were applied to explore the mechanisms by which the IGF-PI3K-AKT pathway was involved in the regulation of osteoclast formation and bone resorption by Trpv6. Results We found that knockout of Trpv6 induced osteoporosis and enhanced bone resorption in mice, but did not affect bone formation. Further studies showed that Trpv6, which was distributed on the cell membrane of osteoclasts, acted as a negative regulator for osteoclast differentiation and function. Mechanistically, Trpv6 suppressed osteoclastogenesis by decreasing the ratios of phosphoprotein/total protein in the IGF–PI3K–AKT signalling pathway. Blocking of the IGF–PI3K–AKT pathway significantly alleviated the inhibitory effect of Trpv6 on osteoclasts formation. Conclusions Our study confirmed the important role of Trpv6 in bone metabolism and clarified its regulatory role in osteoclasts at the cellular level. Taken together, this study may inspire a new strategy for the treatment of osteoporosis.
研究领域:
骨骼生物学
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细胞信号传导
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Zhenting Zhang,Sixiu Zhong,Ruihua Zhang,Qibing Zeng,Pinggui Lei,Wenjin Qiu,Wang Chen,Daoping Wang,Xinjing Wei,Qun Huang,Ting Hu,Peng Luo
Skeletal fluorosis is closely associated with inflammation and metabolic disorders caused by excessive fluoride exposure. Rosa roxburghii Tratt juice (RRTJ), a natural dietary supplement, has been widely used to manage diseases associated with inflammatory damage and metabolic disorders. However, it is largely unknown if RRTJ can mitigate fluoride-induced bone metabolism disorders and the underlying mechanisms. In this study, we demonstrated that RRTJ supplementation significantly improved fluoride exposure-induced bone metabolism disorders, enhanced anti-inflammatory responses, increased short-chain fatty acid concentrations (SCFAs), strengthened the intestinal barrier, and markedly enriched beneficial bacteria, particularly Ligilactobacillus spp. Notably, we identified Rosa roxburghii Tratt polysaccharides (RRTP) as a key component of RRTJ that significantly promotes the growth of Ligilactobacillus murinus . Additionally, RRTJ effectively alleviated fluoride-induced lipid metabolism disorders. A mechanistic study revealed that RRTJ fortifies intestinal barrier function via activating intestinal G-protein-coupled receptor 43 (GPR43) and inhibiting NF-κB signaling pathways, leading to ameliorating bone metabolism disorders. These findings reveal the unique mechanism of RRTJ in balancing bone metabolism and provide new insights into the interaction between natural products and the gut microbiota, offering potential dietary strategies to mitigate fluorosis-induced bone metabolism disorders.
研究领域:
营养学
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微生物学
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药理学
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毒理学
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骨骼生物学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2025
·
IF 20.3
Tianliang Ma,Qimeng Liu,Zheyu Zhang,Jiangyu Nan,Guanzhi Liu,Yute Yang,Yihe Hu,Jie Xie
The onset of periprosthetic osteolysis is mediated by wear particles following artificial arthroplasty. This manifests as a disturbed bone metabolism microenvironment, characterized by insufficient osteogenesis and angiogenesis, and enhanced osteoclastic activity. To target and remodel the homeostatic environment of bone metabolism in the sterile region around the prosthesis, we successfully pioneered the proposal and construction of a fused exosome (f-exo) system with M2 macrophage-derived exosomes (M2-exo) and urine-derived stem cell exosomes (USC-exo). The results demonstrate that f-exo effectively combines the osteolysis region-targeting capabilities of M2-exo with the bone metabolic homeostasis modulation effects of two exosomes (M2-exo and USC-exo), thereby achieving a significantly enhanced bone metabolic homeostasis targeting effect in the periprosthetic osteolysis region. The proteomic analysis of M2-exo, USC-exo, and f-exo revealed the potential mechanism of f-exo in targeting-regulation of bone metabolic homeostasis. Our study employs an innovative approach utilizing the fused exosome system for exosome targeted delivery, which offers a novel intervention strategy for the clinical management of periprosthetic osteolysis. Furthermore, it provides a novel conceptual framework for the development of exosome-based drug-targeting delivery systems.
研究领域:
骨科
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再生医学
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组织工程
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外泌体治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）