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Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

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Nano Research 2024年第4期17卷 2949-2959页

作者： Lin Yang Xueying An Wang Gong Wenshu Wu Bin Liu Xiaoyan Shao Yansi Xian Rui Peng Baosheng Guo Qing Jiang Division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic SurgeryNanjing Drum Tower Hospital Clinical College of Nanjing Medical University321 Zhongshan RoadNanjing 210008China Branch of National Clinical Research Center for Orthopedics Sports Medicine and RehabilitationNanjing 210008China State Key Laboratory of Pharmaceutical Biotechnology Medical SchoolNanjing University&Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal ***,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption ***,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption ***,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast ***,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt *** conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

关键词： osteoporosis α-cyperone osteoclast phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) liposome

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The role and applications of extracellular vesicles in osteoporosis

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Bone Research 2024年第1期12卷 62-77页

作者： Fei Fang Jie Yang Jiahe Wang Tiantian Li Erxiang Wang Demao Zhang Xiaoheng Liu Chenchen Zhou Institute of Biomedical Engineering West China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu 610041China State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China

osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture,which increases patient susceptibility to fragile *** intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles(EVs),which play crucial roles in both pathological and physiological *** derived from various sources exert distinct effects on ***,EVs released by osteoblasts,endothelial cells,myocytes,and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins,miRNAs,and ***,EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone ***,the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is ***,we review the current understanding of the impact of EVs on bone homeostasis,including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in ***,we present an overview of the latest research progress on diagnosing and treating osteoporosis by using ***,we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.

关键词： osteoporosis homeostasis biomaterials

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A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

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Bone Research 2024年第1期12卷 227-239页

作者： Yong Li Zhengwen Cai Wenjuan Ma Long Bai En Luo Yunfeng Lin State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduSichuan 610041PR China Department of Oral and Maxillofacial Surgery Affiliated Stomatological HospitalSouthwest Medical UniversityLuzhouSichuan 646000PR China Sichuan Provincial Engineering Research Center of Oral Biomaterials ChengduSichuan 610041China

Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment *** patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal *** address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of *** synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with *** in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone *** findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

关键词： curcumin osteoporosis diabetic

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The role of lipid metabolism in osteoporosis:Clinical implication and cellular mechanism

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Genes & Diseases 2024年第4期11卷 220-233页

作者： Jing Zhang Wenhui Hu Zhi Zou Yuheng Li Fei Kang Jianmei Li Shiwu Dong College of Bioengineering Chongqing UniversityChongqing 400044China Department of Biomedical Materials Science College of Biomedical EngineeringArmy Medical University(Third Military Medical University)Chongqing 400038China State Key Laboratory of Trauma and Chemical Poisoning Army Medical University(Third Military Medical University)Chongqing 400038China

In recent years,researchers have become focused on the relationship between lipids and bone metabolism ***,many diseases related to lipid metabolism dis-orders,such as nonalcoholic fatty liver disease,atherosclerosis,obesity,and menopause,are associated with osteoporotic *** has been clinically observed in humans that these lipid metabolism disorders promote changes in osteoporosis-related indicators bone mineral density and bone ***,similar osteoporotic phenotype changes were observed in high-fat and high-cholesterol-induced animal *** lipid metabolism(such as increased oxidized lipids and elevated plasma cholesterol)affects bone microenvironment ho-meostasis via cross-organ communication,promoting differentiation of mesenchymal stem cells to adipocytes,and inhibiting commitment towards ***,disturbances in lipid metabolism affect the bone metabolism balance by promoting the secretion of cyto-kines such as receptor activator of nuclear factor-kappa B ligand by osteoblasts and stimulating the differentiation of ***,this review addresses the possible link be-tween lipid metabolism disorders and osteoporosis and elucidates the potential modulatory mechanisms and signaling pathways by which lipid metabolism affects bone metabolism *** also summarize the possible approaches and prospects of intervening lipid meta-bolismforosteoporosistreatment.

关键词： Bone homeostasis Cross-organ communication Lipid metabolism Osteoclast osteoporosis

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Potential therapeutic role of spermine via Rac1 in osteoporosis:Insights from zebrafish and mice

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Zoological Research 2024年第2期45卷 367-380页

作者： Rui-Xue Jiang Nan Hu Yu-Wei Deng Long-Wei Hu Hao Gu Nan Luo Jin Wen Xin-Quan Jiang Department of Prosthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China College of Stomatology Shanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai 200125China Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200011China Department of Preventive Dentistry Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China

osteoporosis(OP)is a prevalent metabolic bone *** drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted *** a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone *** showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone *** not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and ***,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and *** the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of *** findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening *** study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular *** their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

关键词： osteoporosis Spermine Rac1 Zebrafish Mice

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Protective Effects of Phellodendron Species on Bone Health: A Novel Perspective on Their Potentials in Treating osteoporosis and Osteoarthritis

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Chinese Journal of Integrative Medicine 2024年第4期30卷 379-384页

作者： XIN Li TAN Guo-yao ZHANG Qiang ZHANG Qun Good Clinical Practice Development Guangdong Provincial Key Laboratory of Bone and Joint Degeneration DiseasesThe Third Affiliated Hospital of Southern Medical UniversityGuangzhou(510630)China Department of Pharmacy Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou(510120)China

Phellodendron(PN)species,traditionally used in Chinese medicine for centuries,hold promise as a potential treatment for osteoporosis(OP)and osteoarthritis(OA)due to their bioactive *** bioactive compounds,including berberine and palmatine,exhibit anti-inflammatory,antioxidant,and bone-protective properties,contributing to their potential therapeutic benefits in promoting bone health and preventing bone ***,challenges such as the need for standardized preparation and dosing,limited clinical studies,and potential interactions with other medications hinder their clinical ***,the rich history of PN species in Chinese medicine provides a promising foundation for future investigation into their potential as alternative treatments for OP and *** research is needed to fully understand the underlying mechanisms of action and explore the clinical implications of PN for bone health.

关键词： Phellodendron species bone health osteoporosis osteoarthritis review

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Insights and implications of sexual dimorphism in osteoporosis

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Bone Research 2024年第1期12卷 20-49页

作者： Yuan-Yuan Zhang Na Xie Xiao-Dong Sun Edouard C.Nice Yih-Cherng Liou Canhua Huang Huili Zhu Zhisen Shen Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China West China School of Basic Medical Sciences&Forensic Medicine Sichuan UniversityChengdu 610041China Department of Biochemistry and Molecular Biology Monash UniversityClaytonVIC 3800Australia Department of Biological Sciences Faculty of ScienceNational University of SingaporeSingapore 117543Republic of Singapore Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China Hospitaland West China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu 610041China Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education Department of Reproductive MedicineWest China Second University Hospital of Sichuan UniversityChengduChina Department of Otorhinolaryngology and Head and Neck Surgery The Affiliated Lihuili HospitalNingbo University315040 NingboZhejiangChina

osteoporosis,a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture,has led to a high risk of fatal osteoporotic fractures *** evidence has revealed that sexual dimorphism is a notable feature of osteoporosis,with sex-specific differences in epidemiology and ***,females are more susceptible than males to osteoporosis,while males are more prone to disability or death from the *** date,sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone *** the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and *** literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis,mainly in a population of aging patients,chronic glucocorticoid administration,and ***,we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and ***,the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.

关键词： osteoporosis epidemiology overcome

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Hypermethylation of the ALOX12 and CBS promoters in osteoporosis:Potential biomarkers for early diagnosis

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Genes & Diseases 2024年第1期11卷 30-33页

作者： Shang Guo Yue Wu Weekai Chia Peichun Hsu Hongwei Wang Yunliang Wang Biao Zhong Department of Orthopedic Surgery Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200023China Institute of Translational Medicine Shanghai General HospitalShanghai Jiao Tong University School of Medicine(SJTU-SM)Shanghai 200025China The University of Chicago Department of MedicineChicagoIL 60637USA Department of Neurology The Second Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450014China

As a bone-confined chronic degenerative disorder,the progression of osteoporosis is characterized by abnormal crosstalk between osteoblasts and osteoclasts,leading to an imbalance of bone remodeling in adults.1 Several studies reported that arachidonic acid ester 12 lipoxygenase(ALOX12)acts as a regulator in bone genesis by participating in the activation of the peroxisome proliferatoractivated receptor(PPARG)pathway through its reaction product.

关键词： osteoporosis diagnosis remodeling

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Unveiling the role of hypoxia-inducible factor 2alpha in osteoporosis:Implications for bone health

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World Journal of Stem Cells 2024年第4期16卷 389-409页

作者： Ling-Ling Wang Zhan-Jin Lu Shun-Kui Luo Yun Li Zhe Yang Hong-Yun Lu Department of Gerontology The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Department of Endocrinology and Metabolism The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Guangdong Provincial Key Laboratory of Biomedical Imaging The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Department of Endocrinology and Metabolism Zhuhai People’s Hospital(Zhuhai Clinical Medical College of Jinan Universitythe First Hospital Affiliated with Medical College of Macao University of Science and Technology)Zhuhai 519000Guangdong ProvinceChina

BACKGROUND osteoporosis(OP)has become a major public health problem *** OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing *** the bone marrow(BM)niche,bone mesenchymal stem cells(BMSCs)are exposed to a hypoxic ***,a few studies have demonstrated that hypoxiainducible factor 2alpha(HIF-2α)is involved in BMSC osteogenic differentiation,but the molecular mechanism involved has not been *** To investigate the effect of HIF-2αon the osteogenic and adipogenic differentiation of BMSCs and the hematopoietic function of hematopoietic stem cells(HSCs)in the BM niche on the progression of *** Mice with BMSC-specific HIF-2αknockout(Prx1-Cre;Hif-2αfl/fl mice)were used for in vivo *** quantification was performed on mice of two genotypes with three interventions:Bilateral ovariectomy,semilethal irradiation,and dexamethasone ***,the hematopoietic function of HSCs in the BM niche was compared between the two mouse *** vitro,the HIF-2αagonist roxadustat and the HIF-2αinhibitor PT2399 were used to investigate the function of HIF-2αin BMSC osteogenic and adipogenic ***,we investigated the effect of HIF-2αon BMSCs via treatment with the mechanistic target of rapamycin(mTOR)agonist MHY1485 and the mTOR inhibitor *** The quantitative index determined by microcomputed tomography indicated that the femoral bone density of Prx1-Cre;Hif-2αfl/fl mice was lower than that of Hif-2αfl/fl mice under the three intervention *** vitro,Hif-2αfl/fl mouse BMSCs were cultured and treated with the HIF-2αagonist roxadustat,and after 7 d of BMSC adipogenic differentiation,the oil red O staining intensity and mRNA expression levels of adipogenesis-related genes in BMSCs treated with roxadustat were decreased;in addition,after 14 d of osteogenic differentiation,BMSCs treated with roxadusta

关键词： Hypoxia-inducible factor-2α Bone marrow niche Bone mesenchymal stem cells osteoporosis Osteogenic/adipogenic differentiation Mechanistic target of rapamycin signaling pathway

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Prospective Cohort Investigation on Physical Activity of osteoporosis Outcomes(PAOPO)in Jidong:Objectives,Study Design,and Baseline Characteristics

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Biomedical and Environmental Sciences 2024年第9期37卷 1067-1079页

作者： Jingzhi Yang Hao Shen Sicheng Wang Long Bai Zhen Geng Yingying Jing Ke Xu Yuhe Liu Wenqian Wu Hao Zhang Yuanwei Zhang Zuhao Li Chuandong Wang Guangchao Wang Xiao Chen Jiacan Su Institute of Translational Medicine Shanghai UniversityShanghai 200444China Orthopedic Department of Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200092China Department of Orthopedics Trauma Shanghai Zhongye HospitalShanghai 200941China Clinical Research Institute Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

Objective The aim of this study was to investigate the prospective association between physical activity(PA),independently or in conjunction with other contributing factors,and osteoporosis(OP)*** The Physical Activity in osteoporosis Outcomes(PAOPO)study was a community-based cohort investigation.A structured questionnaire was used to gather the participants’sociodemographic *** mineral density(BMD)measurements were performed to assess OP outcomes,and the relationship between BMD and OP was evaluated within this *** From 2013 to 2014,8,471 participants aged 18 years and older were recruited from Tangshan,China’s Jidong *** on their PA level,participants were categorized as inactive,moderately active,or very *** showed higher physical exercise levels than women across the activity *** was significantly higher in the very active group than in the moderately active and inactive *** aged>50 years are at a higher risk of developing OP and *** The PAOPO study offers promising insights into the relationship between PA and OP outcomes,encouraging the implementation of PA in preventing and managing OP.

关键词： osteoporosis Physical activity Risk factors Cohort study

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