BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2020
·
IF 2.985
Yafei Wang,Huimin Liu,Jianmin Wu,Yunjian Liao,Daifeng Lu,Feng Dong,Hongxi Li,Zhitao Zhang,Yongyun Lian
Periprosthetic osteolysis (PIO) caused by wear particles is the main cause of implant failure, which is regulated by nuclear factor κ B receptor activator ligand (RANKL)/osteoprotegerin (OPG) system. At present, there is a lack of effective drugs to prevent or treat PIO. Previous studies have confirmed that DNA methylation is closely related to postmenopausal osteoporosis and can affect the expression of OPG and RANKL . However, the relationship between DNA methylation and PIO is not clear. In this study, we investigated the inhibitory effect of 5-Aza-2-deoxycytidine (AzadC) on osteolysis induced by titanium particles in a mouse model. This inhibition mechanism is achieved by changing the ratio of RANKL/OPG in the osteolysis model. In conclusion, there is a relationship between DNA methylation and PIO. AzadC has a certain inhibitory effect on osteolysis induced by titanium particles. Regulating DNA methylation may be a new way to treat PIO. Our findings lay a foundation for epigenetic understanding and intervention of osteolysis.
研究领域:
骨科
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表观遗传学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 7
·期 3
·1101-1116
·
IF 5.831
Ting-ben Huang,Yong-zheng Li,Ke Yu,Zhou Yu,Ying Wang,Zhi-wei Jiang,Hui-ming Wang,Guo-li Yang
Bone remolding involves the formation of new bone by osteoblasts and the absorption of old bones by osteoclasts. Due to the vital role of osteoblasts and osteoclasts during bone regeneration, it might be feasible to promote osseointegration around the titanium implants by stimulating osteoblasts and inhibiting osteoclasts by modifying the surfaces of the implants. Lithium is used in the treatment of psychiatric patients, and it may be associated with osteogenesis. In this study, lithium was incorporated with sandblasted, large-grit and acid-etched titanium implants via a hydrothermal treatment. In vitro, the nano-scale surface enhanced the adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs). Moreover, the SLA-Li surface displayed a negative effect on the process of osteoclastogenesis. Further mechanism analysis indicated that the canonical Wnt/β-catenin signaling pathway was activated according to the results of RT-PCR and western blotting. More importantly, the RANKL/OPG signaling axis was also involved in these effects on the SLA-Li surface. The experiments in vivo proved that the SLA-Li surface could induce the bone formation and osseointegration during the early osseointegration after the dental implant surgery. These results suggested that bone homeostasis could be manipulated by an SLA-Li surface, which implied that this new surface might serve as a promising material for clinical application in the future.
研究领域:
生物材料
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组织工程
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骨科
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牙科种植学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
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IF 2.2
XiaoRong Meng,Dandan Meng,Chenhui Xiang,Lingling Pu,Xiaofei Yin,Jing Yang
Objective Postmenopausal osteoporosis (PMOP) is a prevalent metabolic bone disorder characterized by decreased bone mineral density and an increased risk of fractures. This study aims to investigate the molecular mechanisms underlying the therapeutic effects of Apelin-13 in PMOP. Methods A PMOP model was established using mouse embryonic pre-osteoblast MC3T3-E1 cells treated with dexamethasone (DEX). A variety of experimental techniques—including MTT assays, Western blotting, flow cytometry, immunofluorescence staining, mitochondrial membrane potential assays, and ELISA—were employed to elucidate the potential mechanisms through which Apelin-13 exerts its therapeutic effects. Results Apelin-13 significantly enhanced osteoblast activity and effectively reversed the inhibitory effects of DEX on cell proliferation. It suppressed apoptosis by modulating the expression of apoptosis-related proteins. Furthermore, Apelin-13 promoted osteogenic differentiation, upregulated osteogenic protein expression, increased alkaline phosphatase (ALP) activity, and facilitated calcium nodule formation. It also improved mitochondrial function by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA), boosting antioxidant enzyme activity, and activating the Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Critically, Apelin-13 was found to regulate the OPG/RANK/RANKL/IGF-1 signaling axis, and its pro-osteogenic effects were significantly enhanced when used in combination with SPA0355. Conclusion Apelin-13 exhibits promising therapeutic potential for PMOP in in vitro models by modulating key processes related to bone metabolism. It achieves this by attenuating mitochondrial oxidative phosphorylation and regulating the OPG/RANK/RANKL/IGF-1 pathway, thereby laying a foundation for future in vivo studies and clinical applications.
研究领域:
骨生物学
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内分泌代谢病学
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分子药理学
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细胞信号转导
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氧化应激与抗氧化
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骨骼系统疾病
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转化医学
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2020
·Vol. 34
·期 3
·3583-3593
·
IF 4.966
Bu Yang,Shangfu Li,Zheng Chen,Feng Feng,Lei He,Bin Liu,Tianwei He,Xuan Wang,Ruiqiang Chen,Zihao Chen,Peigen Xie,Limin Rong
Background Amyloid β peptide (Aβ) is involved in osteoporosis, but the effects of Aβ on osteoblast and bone formation remain unclear. In this study, we investigated the effect of Aβ on bone formation. Methods An animal model of osteoporosis was established by ovariectomy in C57BL/6 mice. The mice received intraperitoneal injection of Aβ. The effect of Aβ on the osteogenic differentiation of human bone marrow stromal stem cells (hBMSCs) and differentiation of both pre-osteoblasts and pre-osteoclasts in a co-culture system were investigated. Results In the animal study, intraperitoneal injection of Aβ for 8 weeks promoted early and late osteogenic differentiation of hBMSCs. Aβ treatment significantly elevated osterix + (osteoblastic) cells but decreased TRAP + cells (osteoclasts) in the distal femur bone. In vitro study showed that Aβ treatment significantly enhanced matrix mineralization and osteogenic markers (Runx2 and osteocalcin). Aβ treatment activated Wnt/β-catenin signaling in hBMSCs. The effect of Aβ was blocked by DKK1 (a Wnt/β-catenin inhibitor) treatment. In the co-culture system, Aβ treatment significantly increased the ALP activities of MC3T3-E1 cells (pre-osteoblasts) but reduced the TRAP + RAW264.7 cells (pre-osteoclasts). Aβ treatment upregulated TCF1 and OPG proteins in MC3T3-E1 cells. Aβ treatment upregulated IκB-α but downregulated NFATc1protein in RAW264.7 cells. These effects were blocked by XAV-939 (a Wnt signaling antagonist), and then rescued by additional Wnt3a (a Wnt agonist). Conclusion Aβ treatment simultaneously promoted osteogenic differentiation via Wnt/β-catenin signaling, and inhibited osteoclasts differentiation via the OPG/RANKL/RANK system, suggesting Aβ is a positive regulator of osteoblast differentiation and bone formation.
研究领域:
生物学
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医学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
·
2021
·Vol. 22
·期 1
·168-175
·
IF 2.837
Sun Lin-Jun,Li Chong,Wen Xiang-hao,Guo Lu,Guo Zi-Fen,Liao Lan-qing,Guo Yu
Background: Icariin (ICA), one of the main effective components isolated from the traditional Chinese herb Epimedium brevicornu Maxim., has been reported to possess extensive pharmacological actions, including enhanced sexual function, immune regulation, anti-inflammation, and antiosteoporosis.
Methods: Our study was designed to investigate the effect of ICA on cell proliferation and differentiation and the molecular mechanism of OPG/RANKL mediated by the Estrogen Receptor (ER) in hFOB1.19 human osteoblast cells. Results: The experimental results show that ICA can stimulate
cell proliferation and increase the activity of Alkaline Phosphatase (ALP), Osteocalcin (BGP) and I Collagen (Col I) and a number of calcified nodules. Furthermore, the mRNA and protein expression of OPG and RANKL and the OPG/ RANKL mRNA and protein expression ratios were upregulated by ICA.
The above-mentioned results indicated that the optimal concentration of ICA for stimulating osteogenesis was 50ng/mL. Subsequent mechanistic studies comparing 50ng/mL ICA with an estrogen receptor antagonist demonstrated that the effect of the upregulated expression is connected with the estrogen
receptor. In conclusion, ICA can regulate bone formation by promoting cell proliferation and differentiation and upregulating the OPG/RANKL expression ratio by the ER in hFOB1.19 human osteoblast cells.
研究领域:
药理学
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细胞生物学
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分子生物学
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内分泌学
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骨科
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DOI
PubMed
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
·
2019
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IF 1.85
Mo Hui,Zhang Ning,Li Huifu,Li Fan,Pu Rong
Cuscuta chinensis Lam. (Convolvulaceae) is an important herbal medicine widely used to improve sexual function, treat osteoporosis, and prevent aging, and has been reported to exhibit anti-osteoporotic effects in vitro. However, the activity of Cuscuta chinensis Lam. on glucocorticoid-induced osteoporosis still remains unclear. The present study aimed to assess the protective effect and the underlying mechanism of action of Cuscuta chinensis extract (CCE) against glucocorticoid-induced osteoporosis in vivo. Sprague-Dawley rats were randomly divided into four groups as follows: control group, osteoporosis group, and 2 CCE-treated osteoporosis groups (100 mg·kg-1·day-1). Blood samples and femur bones were collected for immunohistochemistry, biochemical, mRNA expression, and western blot analysis. HPLC analysis revealed that chlorogenic acid, quercetin, and hyperin were the major constituents of CCE. The results indicated that CCE increased bone length, bone weight, and bone mineral density and suppressed dexamethasone (DEX)-induced reduction in body weight. In addition, TRAP staining indicated that CCE reduced osteoclasts in DEX-induced osteoporosis rats. Mechanistically, CCE treatment alleviated the increase of bone resorption markers and the decline of osteogenic markers, which might be partially mediated by regulation of RANKL/OPG and RunX2 pathways. These results suggest that CCE showed promising effects in the protection against glucocorticoid-induced osteoporosis through protecting osteoblasts and suppressing osteoclastogenesis.
研究领域:
药理学
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骨骼生物学
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中药学
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2026
·
IF 8.8
Chunqing Ai,Lu Wang,Xingchen Ye,Xiaomeng Ren,Shuang Song,Xuelu Li
Fucoidan (GKP) alleviates OVX-induced bone loss by suppressing osteoclastogenesis. • GKP improves systemic metabolism and identifies betaine as a key metabolite effector. • Betaine attenuates osteoclastogenesis by regulating the OPG/RANK/RANKL signaling. Postmenopausal osteoporosis (PMOP), characterized by excessive bone resorption and impaired bone remodeling, remains a significant global health challenge. This study investigated the protective effects of fucoidan from giant kelp (GKP) against PMOP and its underlying mechanisms in ovariectomized mice. GKP supplementation attenuated bone loss by preserving trabecular microarchitecture, normalizing systemic mineral homeostasis, and suppressing osteoclastogenesis, as evidenced by the downregulation of osteoclast-related genes. 16S rRNA gene sequencing revealed that GKP reshaped the gut microbiota by decreasing the Bacteroidota/Firmicutes ratio and enriching beneficial taxa, which promoted short-chain fatty acid production. Targeted metabolomics revealed that GKP induced profound systemic metabolic reprogramming, particularly amino acid metabolism, and identified betaine as a key systemic metabolite effector upregulated following GKP treatment. In vitro assays demonstrated that betaine suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and mitigated inflammation. In vivo validation demonstrated that betaine intervention recapitulated the osteoprotective phenotype observed in GKP-treated mice, which was associated with regulation of the osteoprotegerin/RANKL/RANK signaling axis. These results indicate that GKP exerts anti-osteoporotic effects in association with changes in gut microbiota and systemic metabolism, while betaine-mediated regulation of the OPG/RANKL/RANK signaling may contribute to its osteoprotective activity. Download: Download high-res image (177KB) Download: Download full-size image
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DOI
高影响因子
Food & Function
·
2022
·Vol. 13
·期 11
·6419-6432
·
IF 6.317
Furong Wang,Pengze Rong,Juan Wang,Xiao Yu,Na Wang,Shengyu Wang,Zikai Xue,Junnan Chen,Wenlong Meng,Xin Peng
Osteoporosis (OP) is characterized by the flaccidity of bones or bone bi-disease caused by kidney deficiency. Lindera aggregate has been used to strengthen kidney function in China for thousands of years. It has been approved by Chinese Pharmacopoeia that the root of Lindera aggregata (RLA) can replenish and tonify the kidney, which is thought to be an effective way to alleviate OP. In this study, a network pharmacology approach was applied to explore the active components and potential mechanisms of RLA in osteoporosis treatment. Then, the ethanolic extract of the root of L. aggregata (EERL) was prepared and these predicted results were validated by prednisone-induced zebrafish embryos model. Moreover, the candidate compounds were identified by UPLC-ESI-MS/MS. The anti-OP results showed that EERL could significantly reverse the bone loss of zebrafish induced by prednisone. The mRNA expressions results showed that EERL decreased osteoclast bone resorption by regulating the RANK/RANKL/OPG system. Also, it increased bone formation by regulating the gene expressions of spp1, mmp2, mmp9, runx2b, alp, and entpd5a. Our results demonstrated the reliability of the network pharmacology method, and also revealed the anti-OP effect and potential mechanism of RLA.
研究领域:
药理学
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分子生物学
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中医药学
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斑马鱼研究
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Ningning Jiang,Hui Jin,Kun Yang,Zhongyuan Zhang,Wenshu Xu,Xiaoxue Chen,Zhenhua Zhang,Hui Xu
The present study evaluated the in vitro effect of metformin (Met) and total flavonoids of Rhizoma Drynariae (TFRD) on osteoclasts, osteocytes, and osteoblasts at different stages. We also assessed the effect and mechanism of treatment with Met combined with TFRD on ovariectomy (OVX)-induced osteoporosis in rats. The results showed that Met combined with TFRD significantly promoted the migration of osteoprogenitor cells and stimulated the differentiation and maturation of osteoblast precursor cells. Furthermore, Met combined with TFRD treatment significantly inhibited the osteogenic inhibitor sclerostin (SOST)/dickkopf 1 (DKK1) protein expression and the osteoclast differentiation factor receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in osteocytes. In the in vivo study, Met combined with TFRD effectively reduced bone resorption markers levels, including type-I collagen carboxy-terminal peptide (CTX-1) and tartrate-resistant acid phosphatase (TRAP), and remarkably increased the bone formation marker propeptide of type I procollagen (PINP) level in the serum of rats with osteoporosis. Met combined with TFRD treatment improved bone mineral density (BMD), trabecular microstructure, and mechanical properties of osteoporotic rats. Mechanistically, Met combined with TFRD downregulated SOST and DKK1 levels, and upregulated Wnt10b, β-catenin, runt-related transcription factor 2 (Runx2) et al. Meanwhile, Met combined with TFRD treatment reduced the RANKL/OPG ratio, and reduced the receptor activator of nuclear factor-κB (RANK), nuclear factor of activated T cells c1 (NFATC1), and TRAP levels. In conclusion, Met combined with TFRD ameliorated bone mass in osteoporotic rats through regulating Wnt/β-catenin signaling pathway and OPG/RANKL/RANK axis.
研究领域:
药理学
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骨科
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内分泌学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Shan Shan Qi,Meng Li Shao,Ze Sun,Si Min Chen,Ying Jun Hu,Hong Tao Wang,Tian Kuo Wei,Xing Sheng Li,Hong Xing Zheng
Diabetic osteoporosis (DOP) is one of the complications of diabetes, with high morbidity, and high disability rate. Here, we established a diabetic rat model and administered lycopene to observe its effect on DOP. Our results showed that ten weeks lycopene treatment lowered blood glucose, improved diabetic induced polydipsia, overeating and body weight loss. Lycopene treatment also enhanced bone mineral density, restored bone mechanical and bone Micro-CT parameters of diabetic rats. Subsequently, lycopene decreased serum inflammatory cytokines levels and increased serum anti-oxidant indicators levels. Moreover, lycopene reduced the number of bone marrow adipocytes, and osteoclasts numbers of diabetic rats. The serum bone turnover markers levels were down-regulated after lycopene treatment. Meanwhile, the bone and serum OPG, RUNX 2 expression levels were up-regulated by lycopene in diabetic rats, and the OPG/RANKL ratio was also up-regulated. This study showed that lycopene could ameliorate diabetic induced bone loss via anti-inflammatory, anti-oxidation, and increasing OPG/RANKL ratio in diabetic rats. Lycopene could be used for nutritional intervention in patients with diabetic osteoporosis.
研究领域:
内分泌学
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营养学
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药理学
·
骨科学
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产品关联
DOI
高影响因子
ACS Omega
·
2026
·
IF 5.2
Zhongyan Bao,Juan Du,Yu Gao,Sinian Liu,Nanhai Xiao,Hang Wang,Luoyuan Zhao,Ming Chen,Fengqin Feng,Wei Qu,Qianqian Wang
This study was designed to comprehensively analyze the benefit effect and underlying mechanism of egg yolk-derived peptide VPF (Val-Pro-Phe) in bone development by integrating network pharmacology, molecular docking/dynamics simulation, and zebrafish in vivo experiments. Results demonstrated that VPF exhibited dose-dependent intervention effects within the concentration range of 0.2–10 μg/mL in normal and bone dysplasia zebrafish. Specifically, 0.2 μg/mL of VPF exhibited significant enhancements in total length (TL), mineralization, and swimming distance by 4.01%, 14.00% (P < 0.05), and 7.31% in normal zebrafish model, whereas 1 μg/mL of VPF led to significant increases in the aforementioned indexes by 6.30%, 45.26%, and 51.05% (P < 0.05) in bone dysplasia zebrafish model. Then, network pharmacology revealed that the highest correlation between VPF in improving bone development and osteoclast differentiation pathway, with osteoprotegerin (OPG) being the core node in this pathway. Molecular docking results showed that VPF exhibited the highest binding affinity for OPG, and this interaction was further validated by 200 ns molecular dynamics simulations, which demonstrated the stability of the VPF-OPG complex. Furthermore, VPF upregulated the gene expression of OPG, and downregulated the gene expression of the receptor activator of the NF-κB ligand (RANKL) and TNF receptor-associated factor 6 Gene (TRAF6), and downregulated the RANKL/OPG ratio in zebrafish. These data indicate that VPF alleviates skeletal dysplasia primarily by OPG-mediated suppression of osteoclast differentiation within the OPG/RANKL/RANK axis, thereby supporting its potential value as a functional food ingredient for promoting bone development.
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Kaiwen Yin,Zheng Liu,Chenyu Liao,Jiawei Li,Hao Wang,Kunhua Yang,Li Zhang,Yunfeng Li
The potential for persistent and controllable delivery of osteoprotegerin (OPG) under osteoporotic conditions has become an essential property of bone implants to promote osseointegration and osteogenesis. Herein, a microenvironment-responsive surface coating for titanium (Ti) implants by immobilizing metal-organic frameworks (MOFs) loaded with OPG onto alkali heat-treated Ti surfaces via gelatin (Gel) (AHT-MOF@OPG-GEL) was successfully fabricated. In weakly acidic environment, MOF@OPG can achieve responsive degradation and slow release of zinc ions (Zn2+) and OPG, which not only inhibits osteoclast activity and osteoclastic biomarker expressions, but also potentiates osteoblast proliferation and differentiation in vitro. Moreover, alkali heat treatment was favorable for the hydrophilicity and cell adhesion of the Ti surface. In addition, in vivo experiments in the osteoporotic bone defect model confirmed that the MOF-based functional coating could promote the generation of new bone around the implant, thereby enhancing the bonding strength between the implant and the surrounding bone tissue, and effectively facilitating the osseointegration of the implant with the bone tissue. In conclusion, this study is expected to provide new ideas for improving the osseointegration of implants in osteoporotic conditions.
研究领域:
生物医学工程
·
骨科研究
·
材料科学
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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）