Journal of Environmental Sciences
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2024
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IF 5.9
Long Zhu,Shangjie Zhou,Li Huang,Xiaotian Wang,Yutong Huang,Jiachen Yu,Zaizhao Wang
Bisphenol A (BPA) is a recognized estrogenic endocrine disruptor that poses a threat to the reproductive health of fish. However, it remains unclear whether and how paternal BPA exposure can lead to developmental toxicity in offspring. To explore the potential paternal BPA exposure impacts on craniofacial cartilage growth in offspring, male rare minnows were subjected to BPA and subsequently mated with normal females to produce progeny. Our results demonstrated that paternal BPA exposure resulted in increased malformation and delayed craniofacial cartilage development in the F1 offspring. Furthermore, BPA exposure led to differential expression of 28 miRNAs in paternal sperm in F0 generation (13 upregulated and 15 downregulated), among which 7 miRNAs were involved in the regulation of bone development. BPA also downregulated the expression of bmp2a and Runx1 during F1 embryonic development. The inhibited bmp2a expression might derive from BPA's stimulation of one miRNA, aca-miR-16a-5P, due to bmp2a being one of its target genes. Notably, paternal BPA exposure did not affect craniofacial cartilage development or gonadal development in the F2 generation. Overall, our study sheds light on the molecular mechanisms underlying the impact of paternal BPA exposure on facial chondrogenesis in offspring and provides theoretical support for the ecological protection of fish populations.
研究领域:
环境毒理学
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发育生物学
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分子生物学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Min Chen,Tao Liu,Wenqiang Li,Yingting Li,Puxin Zhong,Huanchen Yan,Jingyin Kong,Weixiang Liang
Background Cartilage-related diseases, such as hypoplastic chondrodysplasia a rare genetic disorder that affects newborns, causing abnormal cartilage development and restricted skeletal growth. However, the development of effective treatment strategies for chondrodysplasia still faces significant challenges due to limitations in the controlled drug delivery, biocompatibility, and biodegradability of nanomedicines.Methods A biodegradable magnesium doped-silicon based-nanoplatforms based on silicon nanoparticles (MON) was constructed. Briefly, the MON was modified with sulfhydryl groups using MPTMS to form MOS. Further engineering of MOS was achieved by incorporating Mg2+ ions through the “dissolution-regrowth” method, resulting in MMOS. Ica was effectively loaded into the MMOS channels, and HA was anchored on the surface of MOS to obtain MMOS-Ica@HA nanoplatforms. Additionally, in vitro cell experiments and in vivo zebrafish embryo models were used to evaluate the effect of the nanoplatforms on cartilage differentiation or formation and the efficiency of treating chondrodysplasia.Results A series of characterization tests including TEM, SEM, DLS, XPS, EDX, and BET analysis validate the successful preparation of MOS-Ica@HA nanoplatforms. The prepared nanoplatforms show excellent dispersion and controllable drug release behavior. The cytotoxicity evaluation reveals the good biocompatibility of MOS-Ica@HA due to the sustained and controllable release of Ica. Importantly, the presence of Ica and Mg component in MOS-Ica@HA significantly promote chondrogenic differentiation of BMSCs via the Smad5/HIF-1α signaling pathway. In vitro and in vivo experiments confirmed that the nanoplatforms improved chondrodysplasia by promoting cartilage differentiation and formation.Conclusion The findings suggest the potential application of the developed biodegradable MMOS-Ica@HA nanoplatforms with acceptable drug loading capacity and controlled drug release in chondrodysplasia treatment, which indicates a promising approach for the treatment of chondrodysplasia.
研究领域:
生物医学工程
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纳米技术
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组织工程
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再生医学
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药学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2021
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IF 6.291
Yajing Wang,Aoyun Li,Khalid Mehmood,Riaz Hussain,Rao Zahid Abbas,M. Tariq Javed,Yung-Fu Chang,Lianmei Hu,Jiaqiang Pan,Ying Li,Lijun Shi,Zhaoxin Tang,Hui Zhang
Long-term exposure to excessive fluoride causes chronic damage in the body tissues and could lead to skeletal and dental fluorosis. Cartilage damage caused by excessive fluoride intake has gained wide attention, but how fluoride accumulation blocks the development of chondrocytes is still unclear. Here, we report a negative correlation between the length and growth plate width after NaF treatments via apoptosis and autophagy, with shrinkage of cells, nuclear retraction, dissolution of chondrocytes. Whereas, fluoride exposure had no significant effect on the number and distribution of the osteoclasts which were well aligned. More importantly, fluoride exposure induced apoptosis of tibial bone through CytC/Bcl-2/P53 pathways via targeting Caspase3, Caspase9, Bak1, and Bax expressions. Meanwhile, the Beclin1, mTOR, Pakin, Pink, and p62 were elevated in NaF treatment group, which indicated that long-term excessive fluoride triggered the autophagy in the tibial bone and produced the chondrocyte injury. Altogether, fluoride exposure induced the chondrocyte injury by regulating the autophagy and apoptosis in the tibial bone of ducks, which demonstrates that fluoride exposure is a risk factor for cartilage development. These findings revealed the essential role of CytC/Bcl-2/P53 pathways in long-term exposure to fluoride pollution and block the development of chondrocytes in ducks, and CytC/Bcl-2/P53 can be targeted to prevent fluoride induced chondrocyte injury.
研究领域:
毒理学
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细胞生物学
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兽医学
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DOI
PubMed
高影响因子
Cell Reports
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2025
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IF 6.9
Zhuo Li,Zhengnan Guo,Zhengmeng Yang,Boguang Yang,Yuan Hu,Xian Xie,Zhixian Zong,Zekun Chen,Kunyu Zhang,Pengchao Zhao,Gang Li,Xuefeng Yang,Liming Bian
Intramembranous ossification, a major bone development process, begins with the condensation of precursor cells through the timely structural adaption of extracellular matrix (ECM) catering to rapid cellular morphological changes. Inspired by this, we design a highly cell-adaptable hydrogel to recapitulate an ECM-dependent mechanotransduction-metabolism-epitranscriptomics axis in mesenchymal stromal cells (MSCs). This hydrogel significantly enhances the E-cadherin-mediated cell-cell interactions of MSCs and promotes glucose uptake and tricarboxylic acid (TCA) cycle activities. We further show that elevated succinate inhibits fat mass and obesity-associated protein (FTO), a N6-methyladenosine (m 6 A) demethylase, thereby enhancing methyltransferase-like 3 (METTL3)-driven m 6 A methylation. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) indicates increased m 6 A methylation of runt-related transcription 2 (Runx2), a key osteogenic signaling factor, promoting osteogenesis of hydrogel-delivered MSCs and bone regeneration in critical-sized bone defects. Our findings reveal the mechanism underlying the critical impact of adaptable ECM structures on tissue development and provide valuable guidance for the design of ECM-mimetic cell carriers to enhance the therapeutic outcomes of regenerative medicine.
研究领域:
细胞生物学
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分子生物学
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再生医学
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DOI
PubMed
高影响因子
DIFFERENTIATION
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2023
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IF 2.9
Yan Guo,Xingyu Chen,Yongzhen Lai,Meng Lu,Chengyong Wang,Yun Shi,Chengyan Ren,Weihui Chen
The development of the hyoid bone is a complex process that involves the coordination of multiple signaling pathways. Previous studies have demonstrated that disruption of the hedgehog pathway in mice results in a series of structural malformations. However, the specific role and critical period of the hedgehog pathway in the early development of the hyoid bone have not been thoroughly characterized. In this study, we treated pregnant ICR mice with the hedgehog pathway inhibitor vismodegib by oral gavage in order to establish a model of hyoid bone dysplasia. Our results indicate that administration of vismodegib at embryonic days 11.5 (E11.5) and E12.5 resulted in the development of hyoid bone dysplasia. We were able to define the critical periods for the induction of hyoid bone deformity through the use of a meticulous temporal resolution. Our findings suggest that the hedgehog pathway plays a crucial role in the early development of the hyoid bone. Additionally, our research has established a novel and easily established mouse model of synostosis in the hyoid bone using a commercially available pathway-selective inhibitor.
研究领域:
发育生物学
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分子生物学
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遗传学
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PubMed
高影响因子
International Journal of Oral Science
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2019
·Vol. 11
·期 1
·1-12
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IF 2.75
Jiang Yuanjing,Zhang Shixian,Mao Chuanqing,Lai Yongzhen,Wu Di,Zhao Hu,Liao Caiyu,Chen Weihui
The Hedgehog (Hh) signalling pathway is essential for cellular proliferation and differentiation during embryonic development. Gain and loss of function of Hh signalling are known to result in an array of craniofacial malformations. To determine the critical period for Hh pathway antagonist-induced frontal bone hypoplasia, we examined patterns of dysmorphology caused by Hh signalling inhibition. Pregnant mice received a single oral administration of Hh signalling inhibitor GDC-0449 at 100 mg•kg − 1 or 150 mg•kg − 1 body weight at preselected time points between embryonic days (E)8.5 and 12.5. The optimal teratogenic concentration of GDC-0449 was determined to be 150 mg•kg − 1 . Exposure between E9.5 and E10.5 induced frontal bone dysplasia, micrognathia and limb defects, with administration at E10.5 producing the most pronounced effects. This model showed decreased ossification of the frontal bone with downregulation of Hh signalling. The osteoid thickness of the frontal bone was significantly reduced. The amount of neural crest-derived frontal bone primordium was reduced after GDC-0449 exposure owing to a decreased rate of cell proliferation and increased cell death.
研究领域:
发育生物学
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分子生物学
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颅面发育
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DOI
PubMed
高影响因子
Advanced Science
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2025
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IF 14.1
Yiwen Zhou,Lili Chen,Miaomiao Han,Peixiang Zhu,Yanyi Wang,Xuanxuan Yu,Tingyu Reng,Huijuan Wang,Baochao Li,Caixia Zhang,Ziwei Huang,Shuang Lin,Guoyun Wang,Jie Ge,Baosheng Guo,Huang Li
Maxillary underdevelopment is a critical component of skeletal Class III malocclusion, closely linked to altered biomechanical signaling. Mechanical stimulation through early facemask protraction can effectively promote maxillary growth, yet the underlying mechanotransduction mechanisms remain unclear. In this study, fibroblast growth factor 9 (FGF9) is identified as a key biomechanical responder in maxillary development. Secreted predominantly by osteocytes, FGF9 interacts with fibroblast growth factor receptor 2 (FGFR2) on preosteoblasts to inhibit osteogenic differentiation. Mechanical stress reduces FGF9 secretion from osteocytes, thereby relieving its inhibitory effect and enhancing osteogenesis. Mechanistically, FGF9 promotes nuclear translocation of FGFR2 in preosteoblasts, which modulates transcription factors ATF5 and NR2F1 to suppress bone formation. In vivo, targeted overexpression of FGF9 in bone tissue led to significant maxillary growth impairment, underlying the pathological impact of disrupted mechanical signaling. These findings reveal a novel osteocyte–preosteoblast axis regulated by FGF9–FGFR2 signaling in response to mechanical stimulation and provide mechanistic insight into how biomechanical forces shape craniofacial development. This pathway offers new mechanistic insights and potential therapeutic targets for correcting craniofacial skeletal abnormalities.
研究领域:
发育生物学
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分子生物学
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生物力学
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颅面遗传学
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骨生物学
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转化医学
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DOI
PubMed
高影响因子
Cell Reports
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2024
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IF 7.5
Weigang Wang,Na Yang,Liangliang Wang,Yuanxiang Zhu,Xiao Chu,Weijie Xu,Yawei Li,Yihai Xu,Lina Gao,Beibei Zhang,Guoqiang Zhang,Qinmiao Sun,Weihong Wang,Qiang Wang,Wenxin Zhang,Dahua Chen
Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.
研究领域:
发育生物学
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分子遗传学
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颅面生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2024
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IF 3.3
Yuhua Zuo,Chao Chen,Fasheng Liu,Hongmei Hu,Si Dong,Qinyuan Shen,Junquan Zeng,Ling Huang,Xinjun Liao,Zigang Cao,Zilin Zhong,Huiqiang Lu,Jianjun Chen
Background The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly. Objective This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides , against dexamethasone-induced osteoporosis and chondrodysplasia. Methods A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors. Results PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5. Conclusion PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.
研究领域:
药理学
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生物学
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医学
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动物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Microbiome
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2024
·Vol. 12
·期 1
·1-24
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IF 13.8
Lyu Zhengtian,Yuan Gaoxiang,Zhang Yuying,Zhang Fengwenhui,Liu Yan,Li Yifan,Li Guang,Wang Ying,Zhang Ming,Hu Yongfei,Guo Yuming,Liu Dan
Background The gut microbiota is a key regulator of bone metabolism. Investigating the relationship between the gut microbiota and bone remodeling has revealed new avenues for the treatment of bone-related disorders. Despite significant progress in understanding gut microbiota-bone interactions in mammals, research on avian species remains limited. Birds have unique bone anatomy and physiology to support egg-laying. However, whether and how the gut microbiota affects bone physiology in birds is still unknown. In this study, we utilized laying hens as a research model to analyze bone development patterns, elucidate the relationships between bone and the gut microbiota, and mine probiotics with osteomodulatory effects. Results Aging led to a continuous increase in bone mineral density in the femur of laying hens. The continuous deposition of medullary bone in the bone marrow cavity of aged laying hens led to significant trabecular bone loss and weakened bone metabolism. The cecal microbial composition significantly shifted before and after sexual maturity, with some genera within the class Clostridia potentially linked to postnatal bone development in laying hens. Four bacterial strains associated with bone development, namely Blautia coccoides CML164, Fournierella sp002159185 CML151, Anaerostipes caccae CML199 (ANA), and Romboutsia lituseburensis CML137, were identified and assessed in chicks with low bacterial loads and chicken primary osteoblasts. Among these, ANA demonstrated the most significant promotion of bone formation both in vivo and in vitro , primarily attributed to butyrate in its fermentation products. A long-term feeding experiment of up to 72 weeks confirmed that ANA enhanced bone development during sexual maturity by improving the immune microenvironment of the bone marrow in laying hens. Dietary supplementation of ANA for 50 weeks prevented excessive medullary bone deposition and mitigated aging-induced trabecular bone loss. Conclusions These findings highlight the beneficial effects of ANA on bone physiology, offering new perspectives for microbial-based interventions for bone-related disorders in both poultry and possibly extending to human health.
Video Abstract Graphical Abstract
研究领域:
微生物学
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骨生物学
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动物科学
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营养学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
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2023
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IF 5.7
Guo Xiaohe,Yang Xiaoxue,Liu Peisheng,Huang Xiaoyao,Gu Yang,Guo Hao,Xuan Kun,Liu Anqi
Introduction: Cleidocranial dysplasia (CCD) is an autosomal-dominant, heritable skeletal and dental disease, involving hypoplastic clavicles, defective ossification of the anterior fontanelle, dentin and enamel hypoplasia, and supernumerary teeth, which can seriously affect the oral and mental health of patients. Amyloid-like protein aggregation, which is established by lysozyme conjugated with polyethylene glycol (Lyso-PEG), forms a mineralized nanofilm layer on a healthy enamel surface. However, whether it can form a remineralization layer in dental tissues from CCD remains unclear.Methods: This study evaluated deciduous teeth from healthy individuals and a patient with CCD. Because pulp and dentin are functionally closely related, stem cells from human exfoliated deciduous teeth (SHED) from CCD patients and healthy individuals were collected to compare their biological properties.Results: The results found that deciduous teeth from patients with CCD exhibited dentin hypoplasia. In addition, the proliferative ability and osteogenic potential of SHED from patients with CCD were lower than those of control individuals. Finally, Lyso-PEG was applied to dentin from the CCD and control groups, showing a similar remineralization-induced effect on the dentin surfaces of the two groups.Conclusion: These results extend our understanding of the dentin and SHED of patients with CCD, exhibiting good caries-preventive capacity and good biocompatibility of Lyso-PEG, thus providing a novel dental therapy for CCD and patients with tooth hypoplasia.
研究领域:
口腔医学
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生物材料
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组织工程
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口腔健康
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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）