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Regulation of bone phosphorus retention and bone development possibly by BMP and MAPK signaling pathways in broilers

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Journal of Integrative Agriculture 2022年第10期21卷 3017-3025页

作者： LIAO Xiu-dong CAO Su-mei LI Ting-ting SHAO Yu-xin ZHANG Li-yang LU Lin ZHANG Ri-jun HOU Shui-sheng LUO Xu-gang Mineral Nutrition Research Division State Key Laboratory of Animal NutritionInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijing 100193P.R.China Poultry Mineral Nutrition Laboratory College of Animal Science and TechnologyYangzhou UniversityYangzhou 225000P.R.China Laboratory of Feed Biotechnology State Key Laboratory of Animal NutritionCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193P.R.China

The bone morphogenetic protein(BMP)and mitogen-activated protein kinase(MAPK)signaling pathways play an important role in regulation of bone formation and development,however,it remains unclear that the effect of dietary different levels of non-phytate phosphorus(NPP)on these signaling pathways and their correlations with bone phosphorus(P)retention and bone development in ***,this experiment was conducted to investigate the effect of dietary P supplementation on BMP and MAPK signaling pathways and their correlations with bone P retention and bone development in broilers.A total of 800 one-day-old Arbor Acres male broilers were randomly allotted to 1 of 5 treatments with 8 replicates in a completely randomized *** 5 treatments of dietary NPP levels were 0.15,0.25,0.35,0.45 and 0.55%or 0.15,0.22,0.29,0.36 and 0.43%for broilers from 1 to 21 days of age or 22 to 42 days of age,*** results showed that extracellular signal-regulated kinase 1(ERK1)mRNA expression in the tibia of broilers on days 14 and 28,phosphorylated-ERK1(p-ERK1)on day 14,and BMP2 protein expression on days 28 and42 decreased linearly(Pbone mineral concentration(BMC),bone mineral density(BMD),bone breaking strength(BBS)and tibia ash were negatively correlated(r=-0.726 to-0.359,Pbone gal protein(BGP)were positively correlated(r=0.405 to 0.665,P<0.01)with ERK1 mRNA and *** 28 days of age,TP,BMC,BMD,BBS and tibia ash were negatively correlated(r=-0.518 to-0.370,P<0.05)with ERK1 mRNA and BMP2 protein,while tibia ALP was positively correlated(r=0.382 to 0.648,P<0.05)with *** results indicated that TP,BMC,BMD,BBS or tibia ash had negative correlations,while tibia ALP and BGP had positive correl

关键词： broiler bone development bone phosphorus retention signaling pathway

Effect of dietary calcium or phosphorus deficiency on bone development and related calcium or phosphorus metabolic utilization parameters of broilers from 22 to 42 days of age

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Journal of Integrative Agriculture 2020年第11期19卷 2775-2783页

作者： YANG Yun-feng XING Guan-zhong LI Su-fen SHAO Yu-xin ZHANG Li-yang LU Lin LUO Xugang LIAO Xiu-dong Mineral Nutrition Research Division Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijing 100193P.R.China Poultry Mineral Nutrition Laboratory College of Animal Science and TechnologyYangzhou UniversityYangzhou 225000P.R.China College of Animal Science and Technology Hebei Normal University of Science and TechnologyQinhuangdao 066004P.R.China

This experiment was conducted to investigate the effect of dietary calcium(Ca)or phosphorus(P)deficiency on bone development and related Ca or P metabolic utilization parameters of broilers from 22 to 42 days of age based on our previous study,which indicated that dietary Ca or P deficiency impaired the bone development by regulating related Ca or P metabolic utilization parameters of broilers from 1 to 21 days of age.A total of 504 one-day-old Arbor Acres male broilers were randomly assigned to 1 of 4 treatments with 7 replicates in a completely randomized design,and fed the normal control and Ca-or P-deficient diets from 1 to 21 days of *** 22 days of age,the broilers were further fed the normal control diet(0.90%Ca+0.35%non-phytate P(NPP)),the P-deficient diet(0.90%Ca+0.18%NPP),the Ca-deficient diet(0.30%Ca+0.35%NPP)or the Ca and P-deficient diet(0.30%Ca+0.18%NPP),*** results showed that dietary Ca or P deficiency decreased(Pbone mineral density(BMD),bone breaking strength(BBS),ash content,tibia ash Ca content and serum P content on days 28 and 42,but increased(Pbone development and related Ca or P metabolic utilization parameters of broilers were the most sensitive to dietary P deficiency,followed by dietary Ca deficiency or Ca and P-deficiency;dietary Ca or P deficiency impaired the bone development possibly by regulating serum Ca and P contents as well as tibia Ca content and ALP activity of broilers from 22 to 42 days of age.

关键词： calcium deficiency phosphorus deficiency bone development metabolic utilization parameter broiler

Role of fibroblast growth factor receptor 1 in the bone development and skeletal diseases

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Journal of Medical Colleges of PLA(China) 2007年第6期22卷 376-384页

作者：李福兵杜晓岚陈林 State Key Laboratory of Trauma Burns and Combined InjuryTrauma CenterInstitute of Surgery Re-search.Duping Hospital.Third Military Medical University

Accumulating data suggest that FGFs/FGFR1 plays essential roles in the bone development and human skeletal diseases. Conditional inactivation of fgfrl caused different phenotypes displaying in different cells or specific organs and revealed some novel functions of FGFR1 in bone development. Fgfrl mutation mainly induced 2 types of human skeletal diseases, craniosynostosis syndrome and dysplasias. Similar mutation of fgfrl in mouse model just mimicked the phenotype that happened in human. These fa- cilitate the investigation on the underlying mechanism of the diseases. Here we mainly focused on the ad- vance of FGFR1 function in the bone development and its mutation caused skeletal diseases.

关键词： fibroblast growth factor receptor 1 bone development skeletal disease conditional inactivation bone fracture

Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis

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Science Bulletin 2024年第13期69卷 2099-2113页

作者： Jianfei Liang Jing Wang Bingdong Sui Yibo Tong Jihua Chai Qin Zhou Chenxi Zheng Hao Wang Liang Kong Haojian Zhang Yi Bai State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyTaikang Center for Life and Medical SciencesWuhan UniversityWuhan 430079China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an 710004China Department of Implant Dentistry College of StomatologyXi’an Jiaotong UniversityXi’an 710004China State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringSchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyDepartment of Oral and Maxillofacial SurgerySchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China Department of Hematology Zhongnan HospitalWuhan UniversityWuhan 430079China Frontier Science Center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan 430079China Taikang Center for Life and Medical Sciences Wuhan UniversityWuhan 430079China

Stem cells remain in a quiescent state for long-term maintenance and preservation of potency;this process requires fine-tuning regulatory *** this study,we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells(SSCs)in skeletogenesis governed by a key regulator,Ptip(also known as Paxip1,Pax interaction with transcription-activation domain protein-1).Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs,and loss of Ptip in type II collagen(Col2)^(+)progenitors causes abnormal activation and differentiation of SSCs,impaired growth plate morphogenesis,and long bone *** also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1(Pgk1)by repressing histone H3 lysine 27 acetylation(H3K27ac)at the promoter ***,inhibition of glycolysis improved the function of SSCs despite Ptip *** the best of our knowledge,this is the first study to establish an epigenetic framework based on Ptip,which safeguards skeletal stem cell quiescence and potency through metabolic *** framework is expected to improve SSC-based treatments of bone developmental disorders.

关键词： Skeletal stem cells bone development Epigenetics Ptip Glycolysis

Single-cell transcriptomic analysis identifies a highly replicating Cd168+ þskeletal stem/progenitor cell population in mouse long bones

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Journal of Genetics and Genomics 2023年第9期50卷 702-712页

作者： Rui-Cong Hao Zhi-Ling Li Fei-Yan Wang Jie Tang Pei-Lin Li Bo-Feng Yin Xiao-Tong Li Meng-Yue Han Ning Mao Bing Liu Li Ding Heng Zhu Basic Medical College of Anhui Medical University HefeiAnhui 230032China Beijing Institute of Radiation Medicine Beijing 100850China Beijing Institute of Basic Medical Sciences Beijing 100850China State Key Laboratory of Experimental Hematology Department of HematologyFifth Medical Center of Chinese PLA General HospitalBeijing 100071China Air Force Medical Center PLABeijing 100142China

Skeletal stem/progenitor cells(SSPCs)are tissue-specific stem/progenitor cells localized within skeletons and contribute to bone development,homeostasis,and ***,the heterogeneity of SSPC populations in mouse long bones and their respective regenerative capacity remain to be further *** this study,we perform integrated analysis using single-cell RNA sequencing(scRNA-seq)datasets of mouse hindlimb buds,postnatal long bones,and fractured long *** analyses reveal the heterogeneity of osteochondrogenic lineage cells and recapitulate the developmental trajectories during mouse long bone *** addition,we identify a novel Cd168þSSPC population with highly replicating capacity and osteochondrogenic potential in embryonic and postnatal long ***,the Cd168þSSPCs can contribute to newly formed skeletal tissues during fracture ***,the results of multicolor immunofluorescence show that Cd168þSSPCs reside in the superficial zone of articular cartilage as well as in growth plates of postnatal mouse long *** summary,we identify a novel Cd168þSSPC population with regenerative potential in mouse long bones,which adds to the knowledge of the tissuespecific stem cells in skeletons.

关键词： Skeletal stem cell scRNA-seq bone development Fracture healing bone regeneration development

The synergistic role of Pu.1 and Fms in zebrafish osteoclast-reducing osteopetrosis and possible therapeutic strategies

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Journal of Genetics and Genomics 2020年第9期47卷 535-546页

作者： Wei Liu Qianqian Di Kailun Li Jing Li Ning Ma Zhibin Huang Jiahao Chen Sheng Zhang Wenqing Zhang Yiyue Zhang Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou510006China Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes Department of Developmental BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou510515China Department of Orthopedics and Traumatology Nanfang HospitalSouthern Medical UniversityGuangzhou510515China

Osteoclasts are bone resorption cells of myeloid origin. Osteoclast defects can lead to osteopetrosis, a genetic disorder characterized by bone sclerosis for which there is no effective drug treatment. It is known that Pu.1 and Fms are key regulators in myelopoiesis, and their defects in mice can lead to reduced osteoclast numbers and consequent osteopetrosis. Yet how Pu.1 and Fms genetically interact in the development of osteoclasts and the pathogenesis of osteopetrosis is still unclear. Here, we characterized pu.1^(G242) D;fms^(j4e1) double-deficient zebrafish, which exhibited a greater deficiency of functional osteoclasts and displayed more severe osteopetrotic symptoms than the pu.1^(G242) Dor fms^(j4e1) single mutants, suggesting a synergistic function of Pu.1 and Fms in the regulation of osteoclast development. We further demonstrated that Pu.1 plays a dominant role in osteoclastogenesis, whereas Fms plays a dominant role in osteoclast maturation. Importantly, treatment with the drug retinoic acid significantly relieved the different degrees of osteopetrosis symptoms in these models by increasing the number of functional osteoclasts. Thus, we report the development of valuable animal models of osteopetrosis, and our results shed light on drug development for antiosteopetrosis therapy.

关键词： Zebrafish bone development Osteoclasts Osteopetrosis Therapeutics

Amomum villosum induces longitudinal bone growth in adolescent female rats

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Journal of Traditional Chinese Medicine 2012年第3期32卷 453-458页

作者： Sun Haeng Lee Ji Young Kim Hocheol Kim Seul Ki Park Cho Young Kim Sun Yong Chung Gyu Tae Chang Department of Pediatrics of Korean Medicine Kyung Hee University Hospital at Gang-dong892 Dongnam-roGangdong-guSeoul 134-727Republic of Korea Department of Herbal Pharmacology College of Korean MedicineKyung Hee University26 Kyungheedae-roDongdaemoon-guSeoul 130-701Republic of Korea Department of Neuropsychiatry of Korean Medicine Kyung Hee University Hospital at Gang-dong892 Dongnam-roGangdong-guSeoul 134727Republic of Korea

OBJECTIVE:This study was conducted to evaluate the effect of Amomum villosum on longitudinal bone ***:Adolescent female Sprague-Dawley rats were divided into 3 groups and treated for 4 days:control(distilled water,p.o.),recombinant human growth hormone(rhGH;100 μg/kg,s.c.),and ***(500 mg/kg,p.o.) *** day 3,tetracycline(20 g/kg,i.p.) was injected for growth plate *** days 2,3 and 4,5-bromo-2'-deoxyuridine(BrdU)(50 mg/kg,i.p.) was injected to label proliferating *** day 5,tibias were dissected and fixed in 4% paraformaldehyde,dehydrated,and sectioned for immunohistochemistry and ***:The rate of bone growth in the *** and rhGH groups increased to(410 ± 44) and(389 ± 46) μm/day(Pbone morphogenetic protein-2 in the *** and rhGH groups were highly expressed in the growth plate as compared with the control samples,indicating increased bone ***:*** could be used to treat growth retardation during adolescence.

关键词： Amomum villosum Growth plate bone development Recombinant human growth hormone

Wnt signaling:Essential roles in osteoblast differentiation,bone metabolism and therapeutic implications for bone and skeletal disorders

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Genes & Diseases 2023年第4期10卷 1291-1317页

作者： Rexhina Vlashi Xingen Zhang Mengrui Wu Guiqian Chen College of Life Science and Medicine Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and BiomedicineZhejiang Sci-Tech UniversityHangzhouZhejiang 310018China Department of Orthopedics Jiaxing Key Laboratory for Minimally Invasive Surgery in Orthopaedics&Skeletal Regenerative MedicineZhejiang Rongjun HospitalJiaxingZhejiang 314001China Institute of Genetics College of Life ScienceZhejiang UniversityHangzhouZhejiang 310058China

Wnt signaling executes an indispensable performance in osteoblast differentiation,bone development,homeostasis,and *** signals trigger the intracellular Wnt signaling cascade to initiate regulating the implication of b-catenin in the bone *** through the novel discoveries done via high-throughput sequencing technologies on ge-netic mouse models,we highlighted the significant contribution of Wnt ligands,co-receptors,inhibitors,their related skeletal phenotypes in mouse models and the similar bone disorders clinically observed in human ***,the crosstalk between Wnt signaling pathway and BMP,TGF-b,FGF,Hippo,Hedgehog,Notch and PDGF signaling pathways is thoroughly demonstrated to be the underlying gene regulatory network that orchestrates osteoblast dif-ferentiation and bone *** also introspected the significance of Wnt signaling transduction in the reorganization of cellular metabolism by stimulating glycolysis,glutamine catabolism,and fatty acid oxidation in osteoblast-lineage cells that display an important reg-ulatory arbor in the cellular bioenergetics of the *** this evaluation,most to date therapeutical approaches towards osteoporosis and other bone maladies found in human beings,are formulated with an aspiration to holistically revamp the present clinical applica-tions involving various monoclonal antibodies therapies that lack specificity,efficacy,and safety into more requisite advanced therapeutics that satisfy these three requirements for further clinical ***,our review provides comprehensive scientific findings related to the fundamental significance of Wnt signaling cascades in skeletal system and the underlying gene regulatory network with other signaling pathways enlightening re-searchers with the possibility to further integrate the identified target molecules into thera-peutic strategies for skeletal disorders treatment in the clinic.

关键词： bone development bone homeostasis Osteoblast differentiation Skeletal disorders Wnt signaling

Dopaminergic effects on in vitro osteogenesis

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bone Research 2015年第3期3卷 130-139页

作者： Dong Joon Lee Henry C Tseng Sing Wai Wong Zhengyan Wang Meng Deng Ching-Chang Ko NC Oral Health Institute School of Dentistry University of North Carolina Duke Eye Center and Department of Ophthalmology Duke University Medical Center Oral Biology Program School of Dentistry University of North Carolina Department of Pediatric Dentistry School of Dentistry University of North Carolina Department of Orthodontics School of Dentistry University of North Carolina

Multiple growth factors（e.g., BMP2, TGF-b1, FGF2） and isolated genes have been shown to improve osteoblastic proliferation and mineralization, advancing bone tissue engineering. Among these factors, both polydopamine（PDA） and dopamine（DA） monomer have recently been reported to increase osteoblast proliferation and mineralization in vitro. Although a well-characterized neurotransmitter, DA＇s role in the bone is unknown. We hypothesize that DA can directly act on osteoblasts, and examined whether osteoblasts express DA receptors that respond to exogenous DA. m RNAs and protein cell lysates were obtained from MC3T3-E1 cells during osteogenic differentiation phase. Reverse transcription polymerase chain reaction and western blot analysis were used to examine the expression of DA receptors, D1–D5. Dose-response effect and time course of DA treatment on cell proliferation, mineralization, and osteogenic differentiation were investigated at pre-determined days. Real-time PCR was performed to investigate whether DA affects osteogenic gene expression（ALP, BSP, OC, OSX, RUNX2, and Collagen1a2） with or without receptor antagonists（SCH233390 and GR103691）. Two-way ANOVA was used for statistical analysis. All five DA receptors（D1, D2, D3, D4, and D5） m RNAs and proteins were expressed in MC3T3-E1 cells. DA treatment increased cell proliferation for up to 7 days（P, 0.05）. Osteogenic mineralization was significantly greater in the DA-treated group than control group（P, 0.05）. Finally, expression of all the osteogenic genes was inhibited by DA receptor antagonists for D1, D3, and D5. Our findings suggest that MC3T3-E1 osteoblasts express functional DA receptors that enhance proliferation and mineralization. PDA is not biologically inert and has important implications in orthopedic applications. Furthermore, osteoblast differentiation might be regulated by the nervous system, presumably during bone development, remodeling, or repair.

关键词： osteogenic differentiation cell proliferation polymerase chain reaction bone tissue engineering western blot analysis statistical analysis bone development gene expression nervous system growth factors in vitro