|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Ciliary parathyroid hormone signaling activates transforming growth factor-βto maintain intervertebral disc homeostasis during aging显示文摘Degenerative disc disease(DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus(NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor(PTH1 R) to the cilia and enhances parathyroid hormone(PTH) signaling in NP cells. PTH induces transcription of integrin α_vβ_6 to activate the transforming growth factor(TGF)-β-connective tissue growth factor(CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH(iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1 R is expressed in both mouse and human NP cells. Importantly,knockout PTH1 R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1 R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD. | Liwei Zheng Yong Cao Shuangfei Ni Huabin Qi Zemin Ling Xin Xu Xuenong Zou Tianding Wu Ruoxian Deng Bo Hu Bo Gao Hao Chen Yusheng Li Jianxi Zhu Francis Tintani Shadpour Demehri Amit Jain Khaled M.Kebaish Shenghui Liao Cheryle A.Séguin Janet L.Crane Mei Wan Hongbin Lu Paul D.Sponseller Lee H.RileyIII Xuedong Zhou Jianzhong Hu Xu Cao | 2018 | Bone Research2018，6，3： | 13 |
| 2 | Self-assemble peptide biomaterials and their biomedical applications显示文摘Inspired by self-assembling peptides found in native proteins,deliberately designed engineered peptides have shown outstanding biocompatibility,biodegradability,and extracellular matrix-mimicking microenvironments.Assembly of the peptides can be triggered by external stimuli,such as electrolytes,temperature,and pH.The formation of nanostructures and subsequent nanocomposite materials often occur under physiological conditions.The respective properties of side chains in each amino acids provide numerous sites for chemical modification and conjugation choices of the peptides,enabling various resulting supramolecular nanostructures and hydrogels with adjustable mechanical and physicochemical properties.Moreover,additional functionalities can be easily induced into the hydrogels,including shearthinning,bioactivity,self-healing,and shape memory.It further broaden the scope of application of self-assemble peptide materials.This review outlines designs of self-assembly peptide(β-sheet,α-helix,collagen-like peptides,elastin-like polypeptides,and peptide amphiphiles)with potential additional functionalities and their biomedical applications in bioprinting,tissue engineering,and drug delivery. | Jun Chen Xuenong Zou | 2019 | Bioactive Materials2019，4，1： | 12 |
| 3 | Simultaneous incorporation of PTH(1-34) and nano-hydroxyapatite into Chitosan/Alginate Hydrogels for efficient bone regeneration显示文摘Tissue regeneration based on the utilization of artificial soft materials is considered a promising treatment for bone-related diseases.Here,we report cranial bone regeneration promoted by hydrogels that contain parathyroid hormone(PTH)peptide PTH(1-34)and nano-hydroxyapatite(nHAP).A combination of the positively charged natural polymer chitosan(CS)and negatively charged sodium alginate led to the formation of hydrogels with porous structures,as shown by scanning electron microscopy.Rheological characterizations revealed that the mechanical properties of the hydrogels were almost maintained upon the addition of nHAP and PTH(1-34).In vitro experiments showed that the hydrogel containing nHAP and PTH(1-34)exhibited strong biocompatibility and facilitated osteogenic differentiation of rat bone marrow mesenchymal stem cells(rBMSCs)via the Notch signaling pathway,as shown by the upregulated expression of osteogenic-related proteins.We found that increasing the content of PTH(1-34)in the hydrogels resulted in enhanced osteogenic differentiation of BMSCs.Implantation of the complex hydrogel into a rat cranial defect model led to efficient bone regeneration compared to the rats treated with the hydrogel alone or with nHAP,indicating the simultaneous therapeutic effect of nHAP and PTH during the treatment process.Both the in vitro and in vivo results demonstrated that simultaneously incorporating nHAP and PTH into hydrogels shows promise for bone regeneration,suggesting a new strategy for tissue engineering and regeneration in the future. | Zhiyuan Zou Le Wang Zhifei Zhou Qing Sun Delong Liu Yan Chen Hao Hu Yu Cai Sixiong Lin Zhengran Yu Bizhi Tan Wei Guo Zemin Ling Xuenong Zou | 2021 | Bioactive Materials2021，6，6： | 7 |
| 4 | A single-cell transcriptome of mesenchymal stromal cells to fabricate bioactive hydroxyapatite materials for bone regeneration显示文摘The osteogenic microenvironment of bone-repairing materials plays a key role in accelerating bone regeneration but remains incompletely defined,which significantly limits the application of such bioactive materials.Here,the transcriptional landscapes of different osteogenic microenvironments,including three-dimensional(3D)hydroxyapatite(HA)scaffolds and osteogenic medium(OM),for mesenchymal stromal cells(MSCs)in vitro were mapped at single-cell resolution.Our findings suggested that an osteogenic process reminiscent of endochondral ossification occurred in HA scaffolds through sequential activation of osteogenic-related signaling pathways,along with inflammation and angiogenesis,but inhibition of adipogenesis and fibrosis.Moreover,we revealed the mechanism during OM-mediated osteogenesis involves the ZBTB16 and WNT signaling pathways.Heterogeneity of MSCs was also demonstrated.In vitro ossification of LRRC75A+MSCs was shown to have better utilization of WNT-related ossification process,and PCDH10+MSCs with superiority in hydroxyapatite-related osteogenic process.These findings provided further understanding of the cellular activity modulated by OM conditions and HA scaffolds,providing new insights for the improvement of osteogenic biomaterials.This atlas provides a blueprint for research on MSC heterogeneity and the osteogenic microenvironment of HA scaffolds and a database reference for the application of bioactive materials for bone regeneration. | Peng Guo Xizhe Liu Penghui Zhang Zhongyuan He Zhen Li Mauro Alini RGeoff Richards Sibylle Grad Martin J.Stoddart Guangqian Zhou Xuenong Zou Danny Chan Wei Tian Dafu Chen Manman Gao Zhiyu Zhou Shaoyu Liu | 2022 | Bioactive Materials2022，7，3： | 3 |
| 5 | Synergistic osteogenic and angiogenic effects of KP and QK peptides incorporated with an injectable and self-healing hydrogel for efficient bone regeneration显示文摘Irregular defects generated by trauma or surgery in orthopaedics practice were usually difficult to be fitted by the preformed traditional bone graft substitute. Therefore, the injectable hydrogels have attracted an increasing interest for bone repair because of their fittability and mini-invasivity. However, the uncontrollable spreading or mechanical failures during its manipulation remain a problem to be solved. Moreover, in order to achieve vascularized bone regeneration, alternatives of osteogenic and angiogenic growth factors should be adopted to avoid the problem of immunogenicity and high cost. In this study, a novel injectable self-healing hydrogel system (GMO hydrogel) loaded with KP and QK peptides had been developed for enhancing vascularized regeneration of small irregular bone defect. The dynamic imine bonds between gelatin methacryloyl and oxidized dextran provided the GMO hydrogel with self-healing and shear-thinning abilities, which led to an excellent injectability and fittability. By photopolymerization of the enclosed GelMA, GMO hydrogel was further strengthened and thus more suitable for bone regeneration. Besides, the osteogenic peptide KP and angiogenic peptide QK were tethered to GMO hydrogel by Schiff base reaction, leading to desired releasing profiles. In vitro, this composite hydrogel could significantly improve the osteogenic differentiation of BMSCs and angiogenesis ability of HUVECs. In vivo, KP and QK in the GMO hydrogel demonstrated a significant synergistic effect in promoting new bone formation in rat calvaria. Overall, the KP and QK loaded GMO hydrogel was injectable and self-healing, which can be served as an efficient approach for vascularized bone regeneration via a minimally invasive approach. | Runze Li Chen Zhou Jun Chen Haotian Luo Ruoyu Li Danying Chen Xuenong Zou Weicai Wang | 2022 | Bioactive Materials2022，7，12： | 2 |
| 6 | LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice显示文摘The LIM domain-containing proteins Pinch1/2 regulate integrin activation and cell–extracellular matrix interaction and adhesion.Here,we report that deleting Pinch1 in limb mesenchymal stem cells(MSCs)and Pinch2 globally(double knockout;dKO)in mice causes severe chondrodysplasia,while single mutant mice do not display marked defects.Pinch deletion decreases chondrocyte proliferation,accelerates cell differentiation and disrupts column formation.Pinch loss drastically reduces Smad2/3 protein expression in proliferative zone(PZ)chondrocytes and increases Runx2 and Col10a1 expression in both PZ and hypertrophic zone(HZ)chondrocytes.Pinch loss increases sclerostin and Rankl expression in HZ chondrocytes,reduces bone formation,and increases bone resorption,leading to low bone mass.In vitro studies revealed that Pinch1 and Smad2/3 colocalize in the nuclei of chondrocytes.Through its C-terminal region,Pinch1 interacts with Smad2/3 proteins.Pinch loss increases Smad2/3 ubiquitination and degradation in primary bone marrow stromal cells(BMSCs).Pinch loss reduces TGF-β-induced Smad2/3 phosphorylation and nuclear localization in primary BMSCs.Interestingly,compared to those from single mutant mice,BMSCs from dKO mice express dramatically lower protein levels ofβ-catenin and Yap1/Taz and display reduced osteogenic but increased adipogenic differentiation capacity.Finally,ablating Pinch1 in chondrocytes and Pinch2 globally causes severe osteopenia with subtle limb shortening.Collectively,our findings demonstrate critical roles for Pinch1/2 and a functional redundancy of both factors in the control of chondrogenesis and bone mass through distinct mechanisms. | Yiming Lei Xuekun Fu Pengyu Li Sixiong Lin Qinnan Yan Yumei Lai Xin Liu Yishu Wang Xiaochun Bai Chuanju Liu Di Chen Xuenong Zou Xu Cao Huiling Cao Guozhi Xiao | 2020 | Bone Research2020，8，4： | 2 |
| 7 | Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration显示文摘It has been proven that the mechanical microenvironment can impact the differentiation of mesenchymal stem cells(MSCs).However,the effect of mechanical stimuli in biofabricating hydroxyapatite scaffolds on the inflammatory response of MSCs remains unclear.This study aimed to investigate the effect of mechanical loading on the inflammatory response of MSCs seeded on scaffolds.Cyclic mechanical loading was applied to biofabricate the cell-scaffold composite for 15 min/day over 7,14,or 21 days.At the predetermined time points,culture supernatant was collected for inflammatory mediator detection,and gene expression was analyzed by qRT-PCR.The results showed that the expression of inflammatory mediators(IL1B and IL8)was downregulated(p<0.05)and the expression of ALP(p<0.01)and COL1A1(p<0.05)was upregulated under mechanical loading.The cell-scaffold composites biofabricated with or without mechanical loading were freeze-dried to prepare extracellular matrix-based scaffolds(ECM-based scaffolds).Murine macrophages were seeded on the ECM-based scaffolds to evaluate their polarization.The ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying enhanced the expression of M2 polarization-related biomarkers(Arginase 1 and Mrc1,p<0.05)of macrophages in vitro and increased bone volume/total volume ratio in vivo.Overall,these findings demonstrated that mechanical loading could dually modulate the inflammatory responses and osteogenic differentiation of MSCs.Besides,the ECM-based scaffolds that were biofabricated with mechanical loading before freeze-drying facilitated the M2 polarization of macrophages in vitro and bone regeneration in vivo.Mechanical loading may be a promising biofabrication strategy for bone biomaterials. | Penghui Zhang Xizhe Liu Peng Guo Xianlong Li Zhongyuan He Zhen Li Martin J.Stoddart Sibylle Grad Wei Tian Dafu Chen Xuenong Zou Zhiyu Zhou Shaoyu Liu | 2021 | Bioactive Materials2021，6，10： | 2 |
| 8 | Experimental anterior lumbar interbody fusion with an osteoinductive bo-vine bone collagen extract显示文摘 | LI Haisheng ZOU Xuenong WOO C | | 0，，8： | 1 |
| 9 | Opposite Regulation of Chondrogenesis and Angiogenesis in Cartilage Repair ECM Materials under Hypoxia显示文摘Although cartilage tissue engineering has been developed for decades, it is still unclear whether angiogenesis was the accompaniment of chondrogenesis in cartilage regeneration. This study aimed to explore the process of anti-angiogenesis during cartilage regenerative progress in cartilage repair extracellular matrix(ECM) materials under Hypoxia. C3H10T1/2 cell line, seeded as pellet or in ECM materials, was added with chondrogenic medium or DMEM medium for 21 days under hypoxia or normoxia environment. Genes and mi RNAs related with chondrogenesis and angiogenesis were detected by RT-q PCR technique on Days 7, 14, and 21. Dual-luciferase report system was used to explore the regulating roles of mi RNAs on angiogenesis. Results showed that the chondrogenic medium promotes chondrogenesis both in pellet and ECM materials culture. HIF1α was up-regulated under hypoxia compared with normoxia(P < 0.05). Meanwhile, hypoxia enhanced chondrogenesis. miR-140-5p exhibited higher expression while miR-146 b exhibited lower expression. The chondrogenic phenotype was more stabilized in the ECM materials in chondrogenic medium than DMEM medium, with lower VEGFα expression even under hypoxia.Dual-luciferase report assays demonstrated that mi R-140-5p directly targets VEGFα by binding its 3′-UTR. Taken together, chondrogenic cytokines, ECM materials and hypoxia synergistically promoted chondrogenesis and inhibited angiogenesis. mi R-140-5p played an important role in this process. | Shaoming Chen Manman Gao Zhiyu Zhou Jiabi Liang Ming Gong Xuejun Dai Tangzhao Liang Jiacheng Ye Gang Wu Lijin Zou Yingjun Wang Xuenong Zou | 2016 | Journal of Materials Science & Technology2016，32，9： | 1 |
| 10 | Mesenchymal stem cell ingrowth and differentiation on coralline hydroxyapatite scaffolds显示文摘 | Tina Mygind Maik Stiehler Anette Baatrup Haisheng Li Xuenong Zou Allan Flyvbjerg Moustapha Kassem Cody Bünger | 2006 | Biomaterials2006，，6： | 1 |
| 11 | An overview on bone protein extract as the new generation of demineralized bone matrix显示文摘Bone protein extract is regarded as the new generation of demineralized bone matrix. The aim of this paper is to describe and characterize the properties of demineralized bone matrix and its new generation product in addition to its application in animal and human studies. Bone protein extract has features of osteoconductivity, osteoinductivity and osteogenicity, which originate from its unique and precise processing. It has exhibited powerful bone formation capacity both in animal experiments and in clinical trials by providing an optimal microenvironment for osteogenesis. Furthermore, not only does it have excellent bio- compatibility, it also has good compatibility with other implant materials, helping it bridge the host and implanted materials. Bone protein extract could be a promising alternative for demineralized bone matrix as a bone graft substitute. | ZHOU ZhiYu ZOU LiJin LI HaiSheng BUNGER Cody ZOU XueNong | 2012 | Science China(Life Sciences)2012，55，12： | 0 |
| 12 | Biomembrane-inspired design of medical micro/nanorobots:From cytomembrane stealth cloaks to cellularized Trojan horses显示文摘Micro/nanorobots are promising for a wide range of biomedical applications(such as targeted tumor,thrombus,and infection therapies in hard-to-reach body sites)because of their tiny size and high maneuverability through the actuation of external fields(e.g.,magnetic field,light,ultrasound,electric field,and/or heat).However,fully synthetic micro/nanorobots as foreign objects are susceptible to phagocytosis and clearance by diverse phagocytes.To address this issue,researchers have attempted to develop various cytomembrane-camouflaged micro/nanorobots by two means:(1)direct coating of micro/nanorobots with cytomembranes derived from living cells and(2)the swallowing of micro/nanorobots by living immunocytes via phagocytosis.The camouflaging with cytomembranes or living immunocytes not only protects micro/nanorobots from phagocytosis,but also endows them with new characteristics or functionalities,such as prolonging propulsion in biofluids,targeting diseased areas,or neutralizing bacterial toxins.In this review,we comprehensively summarize the recent advances and developments of cytomembrane-camouflaged medical micro/nanorobots.We first discuss how cytomembrane coating nanotechnology has been employed to engineer synthetic nanomaterials,and then we review in detail how cytomembrane camouflage tactic can be exploited to functionalize micro/nanorobots.We aim to bridge the gap between cytomembrane-cloaked micro/nanorobots and nanomaterials and to provide design guidance for developing cytomembrane-camouflaged micro/nanorobots. | Jinhua Li Huaijuan Zhou Chun Liu Shuailong Zhang Ran Du Yulin Deng Xuenong Zou | 2023 | Aggregate2023，4，5： | 0 |
| 13 | Kindlin-2 regulates skeletal homeostasis by modulating PTH1R in mice显示文摘In vertebrates,the type 1 parathyroid hormone receptor(PTH1R)is a critical regulator of skeletal development and homeostasis;however,how it is modulated is incompletely understood.Here we report that deleting Kindlin-2 in osteoblastic cells using the mouse 10-kb Dmp1-Cre largely neutralizes the intermittent PTH-stimulated increasing of bone volume fraction and bone mineral density by impairing both osteoblast and osteoclast formation in murine adult bone.Single-cell profiling reveals that Kindlin-2 loss increases the proportion of osteoblasts,but not mesenchymal stem cells,chondrocytes and fibroblasts,in non-hematopoietic bone marrow cells,with concomitant depletion of osteoblasts on the bone surfaces,especially those stimulated by PTH.Furthermore,haploinsufficiency of Kindlin-2 and Pth1r genes,but not that of either gene,in mice significantly decreases basal and,to a larger extent,PTH-stimulated bone mass,supporting the notion that both factors function in the same genetic pathway.Mechanistically,Kindlin-2 interacts with the C-terminal cytoplasmic domain of PTH1R via aa 474–475 and Gsα.Kindlin-2 loss suppresses PTH induction of cAMP production and CREB phosphorylation in cultured osteoblasts and in bone.Interestingly,PTH promotes Kindlin-2 expression in vitro and in vivo,thus creating a positive feedback regulatory loop.Finally,estrogen deficiency induced by ovariectomy drastically decreases expression of Kindlin-2 protein in osteocytes embedded in the bone matrix and Kindlin-2 loss essentially abolishes the PTH anabolic activity in bone in ovariectomized mice.Thus,we demonstrate that Kindlin-2 functions as an intrinsic component of the PTH1R signaling pathway in osteoblastic cells to regulate bone mass accrual and homeostasis. | Xuekun Fu Bo Zhou Qinnan Yan Chu Tao Lei Qin Xiaohao Wu Sixiong Lin Sheng Chen Yumei Lai Xuenong Zou Zengwu Shao Meiqing Wang Di Chen Wenfei Jin Youqiang Song Huiling Cao Ge Zhang Guozhi Xiao | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
| 14 | Function-oriented design:A novel strategy for advanced biomedical materials显示文摘It has always been a dream to construct tissues and even organs for transplantation to replace those with defects caused by diseases or injuries.Tissue engineering is another milestone in the developmental history of life science after cellular and molecular bioscience.Nevertheless,despite decades of rapid de-velopment,tissue-engineered biomaterials have not been widely used clinically.Biomaterials constructed by physical and chemical methods have lots of difficulty in precisely mimicking the macroscopic and mi-croscopic structures of human tissues.The ultimate way to build organoid tissue for regeneration is to enable the cells to take the initiative and build suitable functions.Based on the thoughts of tissue engi-neering,organoid technology holds great potential as a research tool for a wide range of fields,including developmental biology,disease pathology,cell biology,precision medicine,and drug toxicity and efficacy testing.This technology also holds tremendous potential for regenerative medicine,as organoids present the possibility for autologous and allogeneic cell therapy through the replacement of damaged or dis-eased tissues with organoid-propagated tissue or stem cell populations.In this review work,we briefly outlook the development history of organoid technology,summarize the current bottlenecks and the un-derlying reasons,and propose the unified term“function-oriented design in tissue engineering”,a new topic that may provide a solution to overcome these bottlenecks. | Zhiyu Zhou Wentao Wang Jianmin Wang Hongshui Wang Yi Xia Wei Zhang Yuxiao Lai Xiao Lin Yongcan Huang Xuenong Zou Martin J.Stoddart Zhen Li Wei Tian Shaoyu Liu Xinbao Wu Manman Gao Junhong Li Lei Yang Dafu Chen | 2023 | Journal of Materials Science & Technology2023，，14： | 0 |
| 15 | Bone marrow adipoq+ cell population controls bone mass via sclerostin in mice显示文摘Dear editor,The comorbidity of obesity and osteoporosis illustrates the communication and coordination of adipose and bone tissues.Leptin and adiponectin derived from adipocytes regulate osteoblast formation and function to impact bone mass through direct and indirect mechanisms.1 It is known that bone marrow adipocytes(BMA)can control bone mass by modulating the bone morphogenetic protein(BMP)and other signaling pathways.BMAs can secret soluble factors,which impact osteoblasts,osteoclasts,and osteocytes.2 Sclerostin is a potent inhibitor of bone acquisition that antagonizes Wnt/β-catenin signaling. | Huanqing Gao Yiming Zhong Sixiong Lin Qinnan Yan Xuenong Zou Guozhi Xiao | 2023 | Signal Transduction and Targeted Therapy2023，8，8： | 0 |
| 16 | Regulation of hypoxic stress and oxidative stress in bone grafting: Current trends and future perspectives显示文摘Tissue engineering aims to offer large-scale replacement of damaged organs using implants with the com-bination of cells,growth factors and scaffolds.However,the intra/peri-implant region is exposed to se-vere hypoxic stress and oxidative stress during the early stage of implantation with bone graft materials,which endangers the survival,proliferation and differentiation of seed cells within the implants as well as the host cells surrounding the implants.If the bone graft material could spontaneously and intelligently regulate the hypoxic stress and oxidative stress to a moderate level,it will facilitate the vascularization of the implants and the rapid regeneration of the bone tissue.In this review,we will first introduce the signaling pathways of cellular response under hypoxic stress and oxidative stress,then present the clas-sical material designs and examples in response to hypoxic stress and oxidative stress.And finally,we will address the important role of epigenetic mechanisms in the regulation of hypoxic stress and oxida-tive stress and describe the potential applications and prospective smart bone graft materials based on novel epigenetic factors against hypoxic stress and oxidative stress in bone repair.The main content of this review is summarized in the following graphical abstract. | Hao Hu Xiao Liu Jun Chen Shangbin Cui Hualin Yi Gang Wang Renxian Wang Tiansheng Zheng Ben Wan Zhiyu Zhou Yong Wan Manman Gao Dafu Chen Xuenong Zou | 2023 | Journal of Materials Science & Technology2023，，26： | 0 |
| 17 | Biomimetic hydroxyapatite coating on the 3D-printed bioactive porous composite ceramic scaffolds promoted osteogenic differentiation via PI3K/AKT/mTOR signaling pathways and facilitated bone regeneration in vivo显示文摘The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue engineering.The porous architecture of the implanta-tion was essential conditions for bone regeneration.Meanwhile,the design of biomimetic hydroxyap-atite(HAp)coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate osteogenesis.However,bioactive bio-ceramics such asβ-tricalcium phosphate(β-TCP)and calcium sili-cate(CS)with superior apatite-forming ability were reported to present better osteogenic activity than that of HAp.Hence in this study,3D-printed interconnected porous bioactive ceramicsβ-TCP/CS scaf-fold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction,and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells(mBM-SCs)and the potential mechanisms were explored.The results indicated that HAp apatite coating en-hanced cell proliferation,alkaline phosphatase(ALP)activity,and osteogenic gene expression.Further-more,PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular functions.The present results demonstrated that the key molecules of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and mammalian target of rapamycin(mTOR)were activated after the biomimetic hydrox-yapatite coating were constructed on the 3D-printed ceramic scaffolds.Besides,the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor HY-10358.In vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone quality.These results suggest that biomimetic HAp coating constructed on the 3D-printed bioac-tive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration. | Bizhi Tan Naru Zhao Wei Guo Fangli Huang Hao Hu Yan Chen Jungang Li Zemin Ling Zhiyuan Zou Rongcheng Hu Chun Liu Tiansheng Zheng Gang Wang Xiao Liu Yingjun Wang Xuenong Zou | 2023 | Journal of Materials Science & Technology2023，，5： | 0 |
| 18 | Kindlin-2 regulates skeletal homeostasis by modulating PTH1R in mice显示文摘In vertebrates,the type 1 parathyroid hormone receptor(PTH1R)is a critical regulator of skeletal development and homeostasis;however,how it is modulated is incompletely understood.Here we report that deleting Kindlin-2 in osteoblastic cells using the mouse 10-kb Dmp1-Cre largely neutralizes the intermittent PTH-stimulated increasing of bone volume fraction and bone mineral density by impairing both osteoblast and osteoclast formation in murine adult bone.Single-cell profiling reveals that Kindlin-2 loss increases the proportion of osteoblasts,but not mesenchymal stem cells,chondrocytes and fibroblasts,in non-hematopoietic bone marrow cells,with concomitant depletion of osteoblasts on the bone surfaces,especially those stimulated by PTH.Furthermore,haploinsufficiency of Kindlin-2 and Pth1r genes,but not that of either gene,in mice significantly decreases basal and,to a larger extent,PTH-stimulated bone mass,supporting the notion that both factors function in the same genetic pathway.Mechanistically,Kindlin-2 interacts with the C-terminal cytoplasmic domain of PTH1R via aa 474–475 and Gsα.Kindlin-2 loss suppresses PTH induction of cAMP production and CREB phosphorylation in cultured osteoblasts and in bone.Interestingly,PTH promotes Kindlin-2 expression in vitro and in vivo,thus creating a positive feedback regulatory loop.Finally,estrogen deficiency induced by ovariectomy drastically decreases expression of Kindlin-2 protein in osteocytes embedded in the bone matrix and Kindlin-2 loss essentially abolishes the PTH anabolic activity in bone in ovariectomized mice.Thus,we demonstrate that Kindlin-2 functions as an intrinsic component of the PTH1R signaling pathway in osteoblastic cells to regulate bone mass accrual and homeostasis. | Xuekun Fu Bo Zhou Qinnan Yan Chu Tao Lei Qin Xiaohao Wu Sixiong Lin Sheng Chen Yumei Lai Xuenong Zou Zengwu Shao Meiqing Wang Di Chen Wenfei Jin Youqiang Song Huiling Cao Ge Zhang Guozhi Xiao | 2021 | Signal Transduction and Targeted Therapy2021，6，1： | 0 |
| 19 | Biosynthesis of Bioadaptive Materials:A Review on Developing Materials Available for Tissue Adaptation显示文摘Biomaterials are increasingly being evolved to actively adapt to the desired microenvironments so as to introduce tissue integration, reconstruct stability, promote regeneration, and avoid immune rejection.The complexity of its mechanisms poses great challenge to current biomimetic synthetic materials. Although still at initial stage, harnessing cells, tissues, or even entire body to synthesize bioadaptive materials is introducing a promising future. | Junxuan Ma Zhiyu Zhou Manman Gao Binsheng Yu Deming Xiao Xuenong Zou Cody Bvnger | 2016 | Journal of Materials Science & Technology2016，32，9： | 0 |
| 20 | Bioadaptive Nanorod Topography of Titanium Surface to Control Cell Behaviors and Osteogenic Differentiation of Preosteoblast Cells显示文摘Titanium(Ti) nanorods fabricated using selective corrosion of Ti substrate by anodic technology show better biocompatibility with pre-osteoblast cells. The current study investigated the response of the murine pre-osteoblast cell MC3T3-E1 on Ti nanorod topography and untreated Ti surfaces by means of examination of the morphology and osteogenic differentiation responsible for the pre-osteoblast reaction. The morphology of MC3T3-E1 cells was observed using scanning electron microscopy, and alkaline phosphatase(ALP) activity was measured using a colorimetric assay after incubation for 7, 14, and 21 days.The expression of three osteogenic differentiation markers including ALP, osteocalcin(OCN), and collagen type 1A1(COL1A1) and two transcription factors including runt related transcription factor 2(Runx2)and osterix(Osx) at different time points was detected using real-time polymerase chain reaction analysis in both groups. Osx was used to confirm the protein level. The results showed that Ti nanorod surfaces provided prolonged higher levels of ALP activity compared with unmodified Ti surface on the 14 th and 21st days. Gene expression analysis of ALP, OCN, and COL1A1 showed significant upregulation with modified nanorod topography after incubation for 14 and 21 days. Osteogenic transcription factors of Runx2 and Osx exhibited changes consistent with the osteogenic differentiation markers, and this may contribute to the persistently active differentiation of MC3T3-E1 cells in the Ti nanorod group. These results demonstrated that the current nanostructured surface may be considered bioadaptive topography to control cellular behaviors and osteoblast differentiation. The in vivo performance and applicability are further required to investigate osseointegration between implant and host bone in the early stages for prevention of aseptic implant loosening. | Shao Xu Zhiyu Zhou Manman Gao Changye Zou Yinglin Che Bünger Cody Xuenong Zou Lei Zhou | 2016 | Journal of Materials Science & Technology2016，32，9： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员