INTERNATIONAL UROLOGY AND NEPHROLOGY
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2026
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IF 2.2
Chen Huihui,Zhang Guolei,Jin Jingjing,Cheng Mei Juan,Zhang Dongxue,Niu Zhezhe,Zhu Rongfang,Qian Yuetong,Liang Xiangnan,He Lei,Zhou Wei,Zhang Shenglei,Bai Yaling,Xu Jin Sheng
Purpose Vascular calcification (VC) is highly prevalent and a significant cardiovascular risk factor in patients with chronic kidney disease (CKD). Secreted frizzled-related protein 1 (SFRP1) is a secreted glycoprotein closely associated with the Wnt/β-catenin pathway which plays a crucial role in bone formation, but its function and mechanism in VC remain unknown. Methods Serum and radial artery tissues were collected from CKD patients with or without VC. The cellular model of VSMCs’ calcification was established under high-phosphate conditions in vitro. Western blot, qRT-PCR, and immunofluorescence were used to detect SFRP1 expression. The function of SFRP1 was identified by transfection with sh-SFRP1 and pCMV3-SFRP1 plasmid. Results Initially, bioinformatics analysis showed that SFRP1 expression was significantly elevated in high-phosphate-stimulated rat VSMCs. Subsequently, we discovered that the expression of SFRP1 was dramatically increased in the calcified arteries of CKD patients. Functionally, when SFRP1 was knocked down, the calcification process and the expression of Runx2 were attenuated. In contrast, SFRP1 overexpression exacerbated the β-GP-induced VSMCs’ calcification. Mechanistically, we confirmed the activation of Wnt/β-catenin signaling in the in vitro calcification model and this activation was inhibited by SFRP1 knockdown. Furthermore, when the Wnt/β-catenin signaling was enhanced with LiCl, the suppressing effect of SFRP1 knockdown on β-GP-induced osteogenic transdifferentiation of VSMCs was reversed, and calcification was promoted. Conclusion We identified that SFRP1 promoted vascular calcification in CKD partly by regulating the Wnt/β-catenin/Runx2 axis, suggesting that SFRP1 may be a potential biomarker and therapeutic target for VC in CKD.
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高影响因子
Journal of Stomatology Oral and Maxillofacial Surgery
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2022
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IF 2.48
Yi Sun,Jianlu Shi,Xiaoan Luo,Xuehong Xu
Objective Human periodontal ligament stem cells (hPDLSCs) refer to one kind of somatic stem cells that are capable of differentiating into multiple cell kinds and undergoing robust clonal self-renewal. This work was unearthed to elucidate the possible molecular mechanism of miR-142–3p in mediating osteogenic differentiation of hPDLSCs by targeting SGK1 . Methods The hPDLSCs were isolated, cultured, and identified. hPDLSCs were identified by immunofluorescence staining and multiple differentiation ability detection. Cell proliferation ability was assessed by CCK-8 assay. hPDLSCs were induced using osteogenic differentiation medium. ALP activity was detected by alkaline phosphatase (ALP) staining and ALP activity assay, and mineralized nodule formation was determined by alizarin red staining. The expression levels of osteogenic differentiation marker proteins ALP, RUNX2, and OCN were measured by RT-qPCR. miR-142–3p candidate targets were obtained through bioinformatics analysis. The relationship between miR-142–3p and SKG1 was verified. Results miR-142–3p in hPDLSCs after osteogenic induction was down-regulated. Elevated miR-142–3p restricted hPDLSCs proliferation, and diminished ALP activity and mineralized nodule formation, as well as the expression of ALP, RUNX2, and OCN, while miR-142–3p inhibition led to inverse results. miR-142-3p inhibited SKG1 expression. SKG1 overexpression promoted hPDLSC proliferation and osteogenic differentiation, and reversed the inhibitory function of miR-142–3p on hPDLSCs. Conclusion This study highlights that miR-142–3p represses osteogenic differentiation of hPDLSCs by reducing SGK1 expression.
研究领域:
干细胞生物学
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分子生物学
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口腔生物学
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DOI
PubMed
高影响因子
ORAL DISEASES
·
2026
·
IF 3.1
Jiaying Shi,Shuxian Lin,Jiayu Yan,Wanyi Tang,Xiaohua Wu,Shuwen Ding,Siyi Chen,Ruowen Zhao,Junhua Wu
Background Osteoradionecrosis of the jaw (ORNJ) is a severe radiotherapy complication with unclear molecular drivers. CDKN1A/p21 is upregulated by radiation-induced DNA damage, but its role in ORNJ remains unknown. Methods An ORNJ mouse model was established. Single-cell RNA-sequencing of irradiated mandibles was analyzed and validated in vivo. Irradiated jaw bone marrow mesenchymal stem cells (JBMMSCs) were characterized. p21 was inhibited using UC2288 and siRNA. A UC2288-loaded AlgMA hydrogel was developed for local delivery. Results Bone healing was compromised in ORNJ. Radiation induced p21 upregulation in osteogenic lineage cells, which promoted Rb dephosphorylation and aberrant Smad2/3 phosphorylation, thereby suppressing Runx2-mediated osteogenesis. p21 inhibition reversed this cascade and restored osteogenic differentiation. Local delivery of UC2288@AlgMA significantly enhanced bone regeneration. Conclusion p21-related signaling impairs bone healing after irradiation, and local UC2288 delivery via AlgMA hydrogels represents a viable strategy to enhance ORNJ regeneration.
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高影响因子
American Journal of Translational Research
·
2020
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IF 3.375
Runzi Gao,Wenhui Ji,Tianwei Xia,Yanxing Fan,Wei Wei,Le Shi,Jinzhu Liu,Chao Zhang,Lezhen Xue,Jirong Shen
Osteonecrosis of the femoral head (ONFH) is a common disorder that may be idiopathic, caused by trauma, or associated with alcohol or glucocorticoid use. The goals of early treatment include delaying or avoiding hip replacement, but there are no effective treatments for early-stage disease. The aim of the present study was to evaluate the effects of treatment with 3D-printed porous titanium alloy scaffold combined with daily intraperitoneal trans-cinnamaldehyde (TCA) in a dog model of ONFH. Four weeks after creation of the ONFH model, MRI examination of the femoral head showed the characteristic “double line sign” of ONFH, verifying the validity of our model. After another 12 weeks, femoral head specimens were harvested and examined by gross inspection; micro-computed tomography; histologic staining (hematoxylin and eosin; Masson); immunohistochemical analysis and quantitative real-time polymerase chain reaction analysis. Gross inspection of the femoral head in untreated ONFH animals at 16 weeks after model creation showed pale, exfoliating articular cartilage and disordered trabecular bone. Treatment with 3D-printed titanium alloy porous scaffold combined with TCA ameliorated the pathologic ONFH changes and significantly reduced inmature bone tissue as well as imature collagen in the femoral head, as shown by Masson staining. This treatment also increased VEGF, BMP2, β-catenin, b-FGF, and RUNX2 expression and decreased PPARγ expression, compared with untreated ONFH. In conclusion, 3D-printed titanium alloy porous scaffold combined with TCA can effectively improve ONFH, which may be related to local repair. This provides the theoretical basis for a new treatment strategy for ONFH.
研究领域:
骨科
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再生医学
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药理学
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生物医学工程
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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2019
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IF 3.17
Hailin Liu,Xiuli Zhang,Xinglong Zhong,Zehua Li,Shaoai Cai,Pingzhen Yang,Caiwen Ou,Minsheng Chen
The risk of cardiovascular events in patients with chronic kidney disease is tremendously increased due to vascular calcification . Local vascular inflammation significantly promotes vascular calcification. A previous study has shown that puerarin inhibits calcification of mouse vascular smooth muscle cells (VSMCs) in vitro, but whether puerarin can inhibit vascular calcification in vivo and the underlying mechanisms remain unclear. In this study, we found that rat VSMCs treated with calcifying medium showed more mineral deposition, and this effect was inhibited by puerarin in a dose-dependent manner, as detected by alizarin red staining and calcium content assay. Puerarin also prevented the trans-differentiation of VSMCs into osteoblast-like cells, indicated by down-regulation of bone-related genes including Runx2 and BMP2 . In vivo study of uremic rats induced by renal nephrectomy further confirmed the inhibitory effect of puerarin on vascular calcification in uremic rats. Puerarin treatment significantly prevented mineral deposition in rat aortas and down-regulated the expression of Runx2 and BMP2. Furthermore, we detected the levels of pro-inflammatory cytokines including IL-1β, IL-6, IL-18 and TNFα in vitro and in vivo . The levels of IL-1β were remarkably increased in both calcified VSMCs and aortas of uremic rats, while puerarin treatment markedly decreased the expression of IL-1β. In addition, we found that puerarin reduced IL-1β possibly through targeting NLRP3/Caspase1/IL-1β and NF-κB signaling pathways and inhibiting the generation of reactive oxygen species . Taken together, we demonstrated that puerarin has the capability of inhibiting vascular calcification in uremic rats by inhibiting inflammation.
研究领域:
药理学
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心血管疾病
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肾脏疾病
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炎症
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PubMed
高影响因子
BMC BIOLOGY
·
2025
·Vol. 23
·期 1
·1-23
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IF 4.5
Chen Jiangping,Ren Chengyan,Mao Chuanqing,Lai Yongzhen,Lu Meng,Jiang Yuanjing,Chen Weihui
Background The cranial base develops from multipotent mesenchymal cells through endochondral ossification. Genetic ablation of Sonic hedgehog (Shh) or Smoothened (Smo) leads to early apoptosis of cranial base cells, thus limiting the study of their role in the early development of cranial base. Our previous studies have shown that administration of 150 mg/kg Vismodegib (a Smo-specific small molecule antagonist) in E9.5- or E10.5-mice leads to premature mineralization of the skull base synchondroses. In the current study, we further investigated the molecular mechanisms underlying this model.Results Mice exposed to Vismodegib exhibit premature hypertrophic differentiation and osteogenesis of the cranial base synchondroses after E14.5. However, the expression of Patched1 (Ptch1), Gli1, parathyroid hormone-related protein (PTHrP), and Phh3 was not downregulated in exposure mice. We demonstrate that Shh and Wnt signaling pathways were activated in the cranial base region at E10.5. Administration of Vismodegib at E10.5 transiently inhibited Shh signaling in the cranial base area and caused upregulation of β-catenin expression along with ectopic expression of lymphoid enhancer-binding factor 1 (Lef1) and Runx2 in the ventral mesenchymal cells of the cranial base primordium at E12.5. Diverse degrees of cranial base craniosynostosis induced by various doses of Vismodegib suggest a dose-dependent effect of Shh in early basicranium development.Conclusion sThe present experiment suggests that early activation of Shh standardizes normal embryonic development of cranial base after initial morphogenesis, which may be mediated through the “antagonistic” effect of Shh signaling on Wnt signaling. Our study provides new insights into the role of signal-crosstalk in early morphogenesis of the cranial base.
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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细胞生物学
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药理学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
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2022
·Vol. 50
·期 3
·1-13
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IF 5.314
Zhen Shen,Wei Dong,Zehua Chen,Guoqian Chen,Yan Zhang,Zige Li,Haixiong Lin,Huamei Chen,Minling Huang,Ying Guo,Ziwei Jiang
Total flavonoids of Rhizoma Drynariae (TFRD), extracted from the kidney‑tonifying Traditional Chinese medicine Rhizoma Drynariae, can be effective in treating osteoporosis, bone fractures and defects. However, the pharmacological effects of TFRD on the specific vessel subtype CD31hiEmcnhi during distraction osteogenesis (DO) remains unclear. The present study aimed to investigate the effects of TFRD on CD31hiEmcnhi vessels in a rat model of DO. In the present study, tibial DO models were established using 60 rats with a distraction rate of 0.2 mm per day for 20 days. Co‑immunofluorescence staining of CD31 and endomucin (Emcn) was conducted to determine CD31hiEmcnhi vessels. Radiographic, angiographic and histological analyses were performed to assess bone and vessel formation. Tube formation, alkaline phosphatase (ALP) and Von Kossa staining assays were performed to test angiogenesis of endothelial precursor cells (EPCs) and osteogenesis of bone marrow‑derived mesenchymal stem cells (BMSCs). Additionally, expression levels of platelet‑derived growth factor (PDGF)‑BB, VEGF, runt‑related transcription factor 2 (RUNX2) and Osterix (OSX) were determined by western blotting and reverse transcription‑quantitative PCR. The in vivo assays demonstrated that TFRD markedly promoted CD31hiEmcnhi vessel formation during DO, whereas PDGF‑BB neutralizing antibody suppressed vessel formation. Furthermore, the ALP, Von Kossa staining and tube formation assays indicated that TFRD notably elevated the angiogenic capacity of EPCs and osteogenic capacity of BMSCs under stress conditions, which was significantly suppressed by blocking PDGF‑BB. The protein and mRNA levels of PDGF‑BB, VEGF, RUNX2 and OSX were upregulated by TFRD, but downregulated by blocking PDGF‑BB. Thus, TFRD could facilitate CD31hiEmcnhi vessel formation and subsequently enhance angiogenic‑osteogenic coupling to regenerate bone defects during DO via the PDGF‑BB/VEGF/RUNX2/OSX signaling axis, which indicated that CD31hiEmcnhi vessels could be a potential novel therapeutic target for DO, and TFRD may represent a promising drug for promoting bone regeneration in DO by increasing CD31hiEmcnhi vessels.
研究领域:
药理学
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骨科
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分子生物学
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再生医学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
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IF 4.8
Jiale Mao,Houxing Lei,Pingcui Xu,Shuang Liu,Jiwang Zhou,Mingrong Mei,Nani Wang,Xiaoqin Zhang
Ethnopharmacological relevance Melastoma dodecandrum (MD), a traditional ethnomedicine, has been widely used for the treatment of fractures, osteoarthritis, and osteoporosis due to its remarkable anti-inflammatory activity. However, the specific active components responsible for its therapeutic effects on orthopedic conditions remain unidentified. Aim of the study This study aimed to screen and identify key active components in MD using a combination of cell membrane chromatography and mass spectrometry, followed by cellular validation. Materials and methods A TNF-α-induced osteoblast injury model and an osteoblast membrane chromatography screening system were established to select and identify chemical components of MD that directly act on osteoblasts. The protective effects of MD on osteoblasts were assessed by evaluating cell viability, alkaline phosphatase (ALP) activity, cell mineralization and the expression of osteogenesis-related proteins OCN, RUNX2, and the TNF-α receptor protein TNFR1. Validation of the activity of individual components was also conducted. Results MD significantly improved the viability of osteoblasts under TNF-α-induced injury, enhanced ALP activity, stimulated the expression of OCN and RUNX2 proteins, and decreased the expression of TNFR1. Cell membrane chromatography screening identified 32 chemical components, including 21 flavonoids, 6 organic acids, 2 phenylpropanoids, 2 terpenes, and 1 nucleotide. Molecular docking revealed that isovitexin could bind to the specific receptor TNFR1 on the cell membrane. Furthermore, cellular validation demonstrated that isovitexin significantly protected osteoblasts. Conclusions MD and its pharmacologically active component, isovitexin, exhibit protective effects against TNF-α-induced inflammatory injury in osteoblasts, laying a solid foundation for future drug development.
研究领域:
药理学
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民族药理学
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细胞生物学
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质谱学
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色谱学
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PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2022
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IF 3.712
Fan Zhang,Jingxing Li,Chengxiong Gu,Haibo Zhang
Background The role and function of microRNA (miRNA, miR)-140-5p in the calcification of vascular smooth muscle cells (VSMCs) have been explored in this study.Methods The calcium nodules formed in transfected and β-glycerophosphate (β-GP)-treated VSMCs were observed using Alizarin Red S staining, and alkaline phosphatase (ALP) activity was determined. VSMC apoptosis was detected with flow cytometry assay. The target gene of miR-140-5p was predicted and confirmed with dual-luciferase reporter assay. Relative expressions of miR-140-5p, toll like receptor 4 (TLR4) and vascular calcification-related proteins (α-smooth muscle actin, α-SMA; Msh Homeobox 2, MSX2; bone morphogenetic protein 2, BMP2; Kruppel-like factor 4, KLF4; Runt-related transcription factor 2, RUNX2) were measured through quantitative real time polymerase chain reaction (qRT-PCR) and western blot.Results MiR-140-5p upregulation reversed the effects of β-GP on downregulating miR-140-5p and α-SMA expressions, enhancing ALP activity, calcium nodule formation and cell apoptosis, and upregulating levels of MSX2, BMP2, KLF4 and RUNX2. TLR4 was the target of miR-140-5p, and offset the effects of miR-140-5p on β-GP-induced VSMCs.Conclusions MiR-140-5p upregulation represses β-GP-induced calcification of VSMCs via targeting TLR4, providing a potential therapeutic method for vascular calcification.
研究领域:
分子生物学
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心血管疾病
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2023
·Vol. 23
·期 1
·1-11
·
IF 3.9
Cai Weiye,Sun Bin,Song Chao,Liu Fei,Wu Zhengliang,Liu Zongchao
Background In mouse, it was discovered that resveratrol (Res) enhanced osteoporosis (OP) by boosting osteogenesis. Besides, Res can also have an impact on MC3T3-E1 cells, which are crucial for the control of osteogenesis and thus increase osteogenesis. Although some articles have discovered that Res enhanced autophagy to promote the value-added differentiation of MC3T3, it is unclear exactly how this affects the process of osteogenesis in mouse. Therefore, we will show that Res encourages MC3T3-E1 proliferation and differentiation in mouse pre-osteoblasts and further investigate the autophagy-related mechanism for this impact.Methods (1) MC3T3-E1 cells were separated into blank control group and various concentrations (0.01, 0.1, 1, 10, 100µmol/L) of group in order to determine the ideal Res concentration. In the Res group, Cell Counting Kit-8 (CCK-8) was used to measure the proliferation activity of pre-osteoblasts in mice in each group after resveratrol intervention. Alkaline Phosphatase (ALP) and alizarin red staining were used to gauge the degree of osteogenic differentiation, and RT-qPCR was used to measure the expression levels of Runx2 and OCN in the osteogenic differentiation ability of the cells. (2) In the experiment, four groups were set up: the control group, 3MA group, Res group, and Res + 3MA group. To examine cell mineralization, ALP and alizarin red staining were utilized. RT-qPCR and Western blot detection of cell autophagy activity levels and osteogenic differentiation capacity in each group following intervention.Results (1) Resveratrol might increase the number of mice pre-osteoblast, with the impact being most pronounced at 10µmol/L (P < 0.05). The nodules developed substantially more often than in the blank control group, and Runx2 and OCN expressions significantly increased (P < 0.05). (2) In contrast to the Res group, after 3MA purine blocked autophagy, the Res + 3MA group’s alkaline phosphatase staining and the development of mineralized nodules were reduced. Runx2, OCN, LC3II / LC3I expression decreased, p62 expression increased (P < 0.05).Conclusion The present study partially or indirectly demonstrated that Res may, through increased autophagy, induce osteogenic differentiation of MC3T3-E1 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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骨骼研究
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PubMed
高影响因子
American Journal of Translational Research
·
2018
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IF 3.061
Qian Tang,Minji Tong,Gang Zheng,Liyan Shen,Ping Shang,Haixiao Liu
The Masquelet’s induced membrane (IM) technique is widely used to treat large segmental bone defects due to its physical priority and biological function. However, the underlying molecular mechanism of the IM on bone formation remains unknown. In the present study, rat bone marrow-derived mesenchymal stem cells (BMSCs) were used as an in vitro model and bone morphogenetic protein 2 (BMP-2) was used as a positive control to evaluate the effects of the IM on the osteogenic differentiation of BMSCs. Although the IM group did not exhibit a significant increase in the expression of Runt-related transcription factor 2 (Runx2), Collagen I (Col I), osteocalcin (OCN) and alkaline phosphatase (ALP) relative to the BMP-2 administration, the IM was considerably effective compared with the untreated group. Mechanistically, we found that the IM activated the Smad and mitogen-activated protein kinase (MAPK) pathways, which was further confirmed by application of specific inhibitors of Smad1/5/8 (LDN-193189) and ERK1/2 (U0126). After the combined treatment of the IM and LDN-193189 as well as U0126, the IM-induced increase in Runx2, Col I, and OCN expression was significantly inhibited. These results suggest that IM promotes the osteogenic differentiation of rat BMSCs by activating the Smad1/5/8 and MAPK pathways.
研究领域:
骨科
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干细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2025
·
IF 4.2
Yawen Sun,Guangxiao Zhang,Bowen Zhao,Chenxue Fu,Bin Li,Fang Wang,Ming Tian,Minghui Wang,Hai Lin,Haifang Li
Laying hens are prolific egg producers, and the nutrient composition of breeder eggs critically influences the growth and development of offspring chicks. This study investigated the long-term effects of in ovo vitamin D3 injection (IOI-VD3) on bone development in chicks hatched from eggs laid during the late laying stage (68 weeks old, termed eggs-late). Compared to eggs from the peak laying period (44 weeks old, eggs-peak), eggs-late exhibited significantly lower phosphorus (↓7%, P =0.077) and vitamin D3 (↓26.9%, P <0.001). Consequently, chicks from eggs-late demonstrated inferior bone development at both 1 day (lower leg bone weight by 18%, P <0.05) and 4 weeks (reduced bone mineral content by 10%; P <0.05) of age relative to eggs-peak chicks. Notably, IOI-VD3 efficiently improved embryonic and long-term bone growth in late-egg-derived chicks, increasing bone mass by 14% and accelerating growth rate by 10% ( P <0.05). Further in vivo and in vitro analyses revealed that vitamin D3 promoted bone development by activating osteogenesis-related genes ( P <0.05) and suppressing osteoclastogenic markers ( P <0.05), with the vitamin D receptor (VDR) mediating these effects. Chromatin immunoprecipitation (ChIP) assays confirmed that 1,25-(OH)2D3 strengthened VDR binding to promoter regions of RANKL ( P =0.016) and RUNX2 ( P =0.031). In conclusion, this study highlights the disparity in egg quality between late and peak laying periods and its impact on chick bone development. IOI-VD3 ameliorated bone deficits in eggs-late chicks via VDR-dependent mechanisms.
研究领域:
动物科学
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家禽科学
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营养学
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发育生物学
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分子生物学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）