NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2025
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IF 3.1
Liu Wencheng,Liu Rifu,Yang Yue,Cheng Lixue,Feng Xiaobing,Li Qinglei
This study investigated the potential therapeutic effect of kaempferol on osteoporosis by regulating bone homeostasis through the YAP. The ovariectomy model was constructed. The changes in bone and liver tissue were observed through HE staining. Bone metabolism and inflammatory markers were quantitatively analyzed using RT-qPCR and ELISA. Changes in the YAP/NF-κB signaling pathway were detected through Western blot and immunofluorescence. In vitro, the activity and secretion levels of MC3 T3-E1-differentiated osteoblasts were assessed using CCK- 8 and ELISA. The effects of osteoblast-secreted factors on osteoclast-induced differentiation were analyzed using alizarin red staining, phalloidin staining, ELISA, TRAP staining, and SEM. Finally, the regulatory effects of kaempferol on the expression of bone homeostasis in osteoclasts were examined by immunofluorescence and Western blot. Kaempferol treatment improved trabecular bone structure, increased bone density, and modulated bone metabolism by enhancing OPG expression and suppressing TRAP, NFATC1, and RANKL levels. Kaempferol inhibited the activation of the NF-κB pathway and increased YAP expression, reducing inflammatory factors. In vitro, kaempferol promoted osteoblast differentiation and inhibited osteoclast activity. These effects were most pronounced at higher kaempferol doses and were associated with improved bone remodeling and reduced bone resorption. Kaempferol exhibits significant potential for osteoporosis treatment by regulating bone homeostasis, mitigating inflammation through modulating the YAP.
研究领域:
药理学
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骨生物学
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信号通路研究
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Xinhui Wu,Tianlong Wang,Jinhui Zhao,Lei Zhang,Zhiqing Liu,Yixing Chen,Yiping Luo,Yaqi Liu,Yan Chen,Hui Jiang,Dilixiati Duolikun,Junjian Liu,Wentao Cao,Longpo Zheng
The repair of osteoporotic bone defects remains inadequately addressed, primarily due to a disruption in bone homeostasis, characterized by insufficient bone formation and excessive bone resorption. Current research either focuses on promoting bone formation or inhibiting bone resorption, however, the bone repair efficacy of these single-target therapeutic strategies is limited. Herein, a “two-way regulation” bone homeostasis strategy is proposed utilizing piezoelectric composite membranes (DAT/KS), capable of simultaneously regulating osteogenesis and osteoclastogenesis, with high piezoelectric performance, good biocompatibility, and excellent degradability, to promote bone regeneration under osteoporotic conditions. The DAT/KS membrane under ultrasound (US) treatment enables the controlled modulation of piezoelectric stimulation and the release of saikosaponin D (SSD), which promotes osteogenic differentiation while simultaneously inhibiting osteoclast differentiation and function, thereby effectively restoring bone homeostasis and enhancing osteoporotic bone repair. Mechanistic insights reveal the promotion of both canonical and non-canonical Wnt signaling in bone marrow mesenchymal stem cells (BMSCs), which determines their osteogenic differentiation fate, and the downregulation of the NF-κB signaling in bone marrow mononuclear macrophages (BMMs). This study presents optimized sono-piezoelectric biomaterials capable of bidirectionally regulating both osteogenic and osteoclastic differentiation, providing a new potential therapeutic approach for pathological bone injuries.
研究领域:
生物材料学
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骨科医学
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组织工程学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 23
·4735-4745
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IF 6.331
Minqi Wang,Yiqi Yang,Guanghao Chi,Kai Yuan,Feng Zhou,Liang Dong,Haibei Liu,Qinghui Zhou,Weihua Gong,Shengbing Yang,Tingting Tang
Large bone defects face a high risk of infection, which can also lead to bone homeostasis disorders. This seriously hinders the bone healing process; therefore, the help of a dual-functional scaffold that has both anti-infection and bone-homeostasis-regulating capacities is needed in the treatment of infected bone defects. In this study, a 3D printed dual-functional scaffold composed of poly-ε-caprolactone (PCL), mesoporous bioactive glasses (MBG), and gallium (Ga) was produced. In vitro experiments demonstrated the excellent antibacterial ability of the PCL/MBG/Ga scaffold against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). The scaffold also significantly inhibited osteoclastic activity and promoted osteogenic differentiation. Furthermore, a rabbit model with an infected bone defect in the radius was used to evaluate the in vivo bone healing capability of PCL/MBG/Ga. The results demonstrate that the PCL/MBG/Ga scaffold can significantly accelerate bone healing and prevent bone resorption, suggesting its potential for application in repairing infected bone defects.
研究领域:
生物材料学
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骨科医学
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再生医学
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DOI
PubMed
高影响因子
NPG Asia Materials
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2024
·Vol. 16
·期 1
·1-17
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IF 8.6
Su Shenghui,Xie Jiajun,Gao Jian,Liu Shencai,Dong Xieping,Li Jianwei,Gao Zhong Feng,Chen Keyuan,Liu Weilu
Patients suffering from osteoporotic fractures often require effective fixation and subsequent bone repair. However, the currently available materials are functionally limited and often fail to improve outcomes in this patient population. In this study, we developed orthopedic adhesives doped with romosozumab-loaded mesoporous bioactive glass nanoparticles to aid in osteoporotic fracture fixation and restore dysregulated bone homeostasis. These adhesives were designed to promote osteoblast formation while simultaneously inhibiting osteoclastic bone-resorbing activity, thus working synergistically to promote the healing of osteoporotic fractures. Orthopedic adhesives exhibit injectability, reversible adhesiveness, and malleability, enhancing their adaptability to complex clinical scenarios. Furthermore, the release of romosozumab from mesoporous bioactive glass nanoparticles accelerated osteogenesis and inhibited osteoclastogenesis, delaying the bone resorption process. This dual action contributes to the regulation of bone regeneration and remodeling. Notably, our orthopedic adhesive could restore the disrupted bone homeostasis associated with osteoporotic fractures.
研究领域:
骨科
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生物材料学
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再生医学
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产品关联
DOI
高影响因子
Advanced Science
·
2025
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IF 14.1
Chengzhong Xu,Sijie Qiu,Zhigen Yuan,Chongyin Qiu,Wenyu Xu,Jialiang Guo,Gen Wen,Shuai Liu,Wenjuan Yan,Haibing Xu,Honghao Hou,Dehong Yang
Osteoporotic tendon-to-bone interface healing is challenging, with a high surgical repair failure rate of up to 68%. Conventional tissue engineering approaches have primarily focused on promoting interface healing by stimulating regeneration in either the tendon or bone. However, these methods often fall short of achieving optimal therapeutic outcomes due to their neglect of balancing bone homeostasis and remodeling the microstructure at the osteoporotic tendon-to-bone interface. Herein, a series of site-specific functional modifications are carried out on teriparatide to develop recombinant human parathyroid hormone (R-PTH). A biomimetic microstructured reconstruction scaffold (BMRP) is constructed using a decalcified mussel shell scaffold, pre-gel, and R-PTH. The BMRP mimics the microstructures of the native tendon-to-bone interface and restores the original structure of the interface tissue by repairing injured cells, balancing bone homeostasis, and remodeling the microstructure of the osteoporotic tendon-to-bone interface. In an osteoporotic rotator cuff tear model, BMRP is in situ implanted at the injured site, resulting in structural reconstruction and functional recovery. The BMRP demonstrates excellent repair effects, representing a novel therapeutical alternative for treating osteoporotic tendon-to-bone injury potential for clinical application.
研究领域:
组织工程学
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再生医学
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骨科
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药理学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2025
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IF 4.1
Zizheng Liu,Huiming Jiang,Zhaofeng Zhang,Ruiyang Jiang,Rongliang Wang,Jiawei Li,Weitong Li,Guihua Tan,Yuxiang Fei,Zhongyang Lv,Hu Guo,Ziyin Sun,Rui Wu,Hongfei Shi,Dongquan Shi
Chondrocytes experience adverse lipid metabolism disorders during the degeneration of cartilage in osteoarthritis (OA), while the underlying mechanisms remain poorly understood. SESN2, a highly conserved stress-inducible protein, plays a crucial role in regulating lipid metabolism. This study aims to investigate the role of SESN2 in the regulation of fatty acid metabolism in chondrocytes and elucidate the underlying molecular mechanisms in OA. The expression of SESN2 was significantly decreased in OA-affected human cartilage, and this decrease correlated with the upregulation of lipogenic enzymes. Sesn2 inhibited lipogenic enzyme expression in chondrocytes and improved cartilage homeostasis. Mechanistically, SESN2 inhibited the expression of SREBP1 and interacted with SCAP to deactivate SREBP1-mediated transcription for lipogenesis. Finally, overexpression of Sesn2 in mice undergoing DMM surgery ameliorated OA pathological manifestations and improved behavioral experiments performance through inhibiting fatty acid synthesis. Our findings revealed that SESN2 suppresses SREBP1-mediated transcription for lipogenic enzyme in chondrocytes and ameliorates OA progression. These results highlighted that targeting SESN2 may serve as a promising therapeutic strategy for OA.
研究领域:
分子生物学
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生物化学
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细胞生物学
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骨科
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医学研究
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2025
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IF 7.3
Ziyan Wang,Wei Zhang,Ziyan Liu,Danyang Huang,Huiwen Kang,Jingyu Wang,Guangyu Jiang,Ai Gao
BDE-209 has a causal relationship with adverse health outcomes. However, research on its effect on bone homeostasis is relatively lacking. This study examined the relationship between BDE-209 exposure and bone health, as well as the underlying mechanisms, using both in vitro and in vivo models. In animal studies, female SD rats were administered BDE-209 for 60 days. Bone mineral density, bone microstructure, gut microbiota, and inflammaging markers were measured. Furtherly, THP-1 cell-derived macrophages were treated with a culture medium containing population-relevant dose of BDE-209 or sodium butyrate. The expression of M1 macrophage markers, osteoclast markers, and inflammatory cytokines was measured. Then macrophages were induced by osteoclast conditioned medium to evaluate the effect of BDE-209 on their differentiation into osteoclasts. Results showed reduced humeral bone density, enhanced osteoclast activity, upregulation of IL-1β, TNF-α, IL-6, and activation of PGC-1α/NAD + /cGAS-STING in the exposed group. 16s sequencing revealed that BDE-209 disrupts the abundance of the gut microbiota, notably a reduction in Lachnospiraceae . In vitro, BDE-209 can stimulate macrophages to differentiate more osteoclasts and activate the cGAS-STING pathway, while sodium butyrate can inhibit these effects. This study reveals that gut microbiota dysbiosis is involved in BDE-209-induced bone homeostasis disorder through inflammatory aging and sodium butyrate can mitigate this effect. Overall, this study provides research data for the precaution and treatment of osteoporosis associated with BDE-209 exposure.
研究领域:
毒理学
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免疫学
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骨生物学
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微生物学
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药理学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Yan Huang,Maowen Chen,Yiding Shen,Xinkun Shen,Menghuan Li,Yanan Li,Yuan Liu,Kaiyong Cai,Zhong Luo,Yan Hu
Osteoporosis is a common bone disease characterized by the systemic disruption of hone homeostasis, where the imbalance between bone resorption and formation causes deterioration of bone structure and bone mass loss. Targeted restoration of bone hemostasis has thus become a promising strategy for osteoporosis treatment. For this purpose, we report a bone-targeted nanoformulation based on CaCO 3 nanomaterials, which could be activated in the acidic osteoporotic microenvironment and cooperatively regulate the activity of osteoclasts and osteoblasts to reverse bone deterioration. Herein, a clinical antiosteoporosis drug β-estradiol (E2) is first biomineralized using CaCO 3 to form physiologically stable nanocores. Meanwhile, azido groups are introduced onto MC3T3-E1 cells through incubation with AC 4 ManNAz. The azido-tagged MC3T3-E1 cell membranes are extracted for the camouflaging of the CaCO 3 @E2 nanocores to enhance their in vivo stability and availability, while also enabling the surface modification of bone-targeting dibenzocyclooctyne-tagged alendronate moieties via copper-free click reaction. After the selective deposition into acidic osteoporotic bone tissues, the CaCO 3 @E2 cores would be spontaneously degraded to release E2 and Ca 2+ ions, which would systematically inhibit the activity of osteoclasts while promoting osteoblast-mediated new bone formation, eventually ameliorating the osteoporosis symptoms. This study offers an effective approach for osteoporosis treatment in the clinics.
研究领域:
药理学
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纳米医学
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骨骼生物学
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药物递送系统
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产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Xinchan Liu,Yubo Hou,Mingxi Yang,Xirui Xin,Yu Deng,Ruobing Fu,Xingchen Xiang,Niuben Cao,Xiaomeng Liu,Weixian Yu,Bai Yang,Yanmin Zhou
Periodontitis is a type of chronic inflammatory oral disease characterized by the destruction of periodontal connective tissue and progressive alveolar bone resorption. As oxidative stress is the key cause of periodontitis in the early periodontal microenvironment, antioxidative therapy has been considered a viable treatment for periodontitis. However, more stable and effective reactive oxygen species (ROS)-scavenging nanomedicines are still highly needed due to the instability of traditional antioxidants. Herein, a new type of N -acetyl- l -cysteine (NAC)-derived red fluorescent carbonized polymer dots (CPDs) has been synthesized with excellent biocompatibility, which can serve as an extracellular antioxidant to scavenge ROS effectively. Moreover, NAC-CPDs can promote osteogenic differentiation in human periodontal ligament cells (hPDLCs) under H 2 O 2 stimulation. In addition, NAC-CPDs are capable of targeted accumulation in alveolar bone in vivo, reducing the level of alveolar bone resorption in periodontitis mice, as well as performing fluorescence imaging in vitro and in vivo. In terms of mechanism, NAC-CPDs may regulate redox homeostasis and promote bone formation in the periodontitis microenvironment by modulating the kelch-like ECH-associated protein l (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. This study provides a new strategy for the application of CPDs theranostic nanoplatform for periodontitis.
研究领域:
牙科学
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纳米医学
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分子生物学
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药学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Kui Xu,Caiyun Mu,Chi Zhang,Sijie Deng,Shan Lin,Linlin Zheng,Weizhen Chen,Qiqing Zhang
Improving the ability of implants to integrate with natural bone tissue at the initial stage of implantation remains a huge challenge because bone-to-implant interfaces are often accompanied by abnormal microenvironments with infection, reactive oxygen species (ROS) and unbalanced bone homeostasis. In this study, a multifunctional coating was fabricated on the basis of gallium (III)-phenolic networks. It is easily obtained by immersing the implants into a mixed solution of tannic acids (TAs) and gallium ions. The thickness of the coating can be precisely controlled by adjusting the number and time of immersion experiments. The resulting coating displays excellent near-infrared photothermal property. As the coating degrades, TAs and gallium ions with low concentration are released from the coating, which is more rapid in acidic and oxidative stress microenvironments. Photothermal performance as well as released TAs and gallium ions give the coating outstanding broad-spectrum antibacterial ability. Furthermore, the coating effectively reduces intracellular ROS of osteoblasts. In vitro and in vivo experiments demonstrate the capability of the coating enhancing implants’ osseointegration via pro-osteogenesis and inhibiting osteoclastogenesis. The findings imply that gallium (III)-phenolic coating holds great promise to promote implant osseointegration by rescuing abnormal microenvironments of infection, oxidative stress and unbalanced bone homeostasis.
研究领域:
生物材料
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生物医学工程
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骨科
·
材料科学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Ya Ren,Weiqing Kong,Yihao Liu,Xue Yang,Xiang Xu,Lei Qiang,Xuelian Mi,Changru Zhang,Haoyi Niu,Chengwei Wang,Jinwu Wang
Bone defect repair remains a major clinical challenge that requires the construction of scaffolds that can regulate bone homeostasis. In this study, a photo-cured mesoporous bioactive glass (PMBG) precursor is developed as a tricalcium phosphate (TCP) agglomerant to obtain a double-phase PMBG/TCP scaffold via 3D printing. The scaffold exhibits multi-scale porous structures and large surface areas, making it a suitable carrier for the loading of parathyroid hormone (PTH) (1-34), which is used for the treatment of osteoporosis. In vitro and in vivo results demonstrate that PMBG/TCP scaffolds coordinated with PTH (1-34) can regulate bone homeostasis in a bidirectional manner to facilitate bone formation and inhibit bone resorption. Furthermore, bidirectional regulation of bone homeostasis by PTH (1-34) is achieved by inhibiting fibrogenic activation protein (FAP). Thus, PMBG/TCP scaffolds coordinated with PTH (1-34) are viable materials with considerable potential for application in the field of bone regeneration and provide an excellent solution for the design and development of clinical materials.
研究领域:
生物医学工程
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材料科学
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再生医学
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骨科
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产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2022
·Vol. 6
·期 2
·2200149
·
IF 5.003
Kai Zhang,Junlong Da,Jianqun Wang,Lixue Liu,Xinpeng Liu,Haoze Yuan,Lili Jiang,Yawei Geng,Xiaoyao Liu,Zhuling Jiang,Han Jin,Ying Li,Bin Zhang
Bone damage results from the imbalance of bone homeostasis maintained by osteoblast-regulated bone formation and osteoclast-mediated bone resorption. Conventional drug therapy and gene therapy may not optimally regulate the bone remodeling process due to the unitary pharmacological mechanism of drug and the safety and targeting of gene vectors. In the present study, multifunctional fluorescent alendronate-polyethyleneimine carbon dots (Alen-PEI CDs) are innovatively synthesized, which have excellent biocompatibility, selective bone targeting, gene carrying capacity, and anti-bone absorption effect. As gene vectors, bone morphogenic protein 2 (BMP2) gene-loaded Alen-PEI CDs greatly enhance osteoblast differentiation and bone regeneration. Notably, Alen-PEI CDs are found to directly inhibit the formation and function of osteoclasts, effectively attenuating the LPS-induced skull osteolysis in mice. Furthermore, their cumulative toxicity is lower than that of Alen, indicating their potential as an anti-bone resorptive nanodrug. These results show that the bone-targeting Alen-PEI CDs significantly reverse the imbalance of bone homeostasis through a dual-directional mechanism—directly suppressing bone resorption and indirectly inducing bone formation by transfection of osteogenic therapeutic genes. Overall, the study expands the application for carbon dots in biomedicine, providing new insights for the further development of novel selectively targeted multifunctional nanodrugs for the treatment of bone-destructive diseases.
研究领域:
生物医学工程
·
药学
·
分子生物学
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组织工程
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纳米技术
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）