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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu sherwin Ho Michael J.Lee jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu sherwin H.Ho jason Strelzow Russell R.Reid Tong-Chuan He Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine

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Genes & Diseases 2019年第3期6卷 201-223页

作者： Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago MedicineChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Rosalind Franklin University Chicago Medical SchoolNorth ChicagoIL 60064USA SIR Program Illinois Math and Science Academy(IMSA)AuroraIL 60506USA Department of Biomedical Engineering Northwestern UniversityEvanstonIL60208USA The Department of Surgery Feinberg School of MedicineNorthwestern UniversityChicagoIL60616USA

Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological *** roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ *** of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP *** it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other *** effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of ***,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and *** review aims to summarize our current understanding of BMP9 across biology and the body.

关键词： Adipogenesis Bone morphogenetic proteins(BMPs) BMP9/GDF2 Mesenchymal stem cells(MSCs) Metabolism Osteogenesis Regenerative medicine Tumorigenesis

Notch signaling:Its essential roles in bone and craniofacial development

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Genes & Diseases 2021年第1期8卷 8-24页

作者： Mikhail Pakvasa Pranav Haravu Michael Boachie-Mensah Alonzo Jones Elam Coalson Junyi Liao Zongyue Zeng Di Wu Kevin Qin Xiaoxing Wu Huaxiu Luo Jing Zhang Meng Zhang Fang He Yukun Mao Yongtao Zhang Changchun Niu Meng Wu Xia Zhao Hao Wang Linjuan Huang Deyao Shi Qing Liu Na Ni Kai Fu Michael J.Lee Jennifer Moriatis Wolf Aravind Athiviraham sherwin S.Ho Tong-Chuan He Kelly Hynes jason Strelzow Mostafa El Dafrawy Russell R.Reid Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Pritzker School of Medicine University of ChicagoChicagoIL 60637USA Section of Plastic and Reconstructive Surgery Department of SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Departments of Orthopaedic Surgery Gastrointestinal SurgeryObstetrics and Gynecologyand NephrologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016PR China Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory and Diagnostic MedicineChongqing Medical UniversityChongqing400016PR China Department of Burn and Plastic Surgery West China Hospital of Sichuan UniversityChengduSichuan610041PR China Department of Orthopaedic Surgery The First Affiliated HospitalGuangzhou University of Chinese MedicineGuangzhouGuangdong510405PR China Departments of Orthopaedic Surgery and Neurosurgery The Affiliated Zhongnan Hospital of Wuhan UniversityWuhanHubei430072PR China Department of Orthopaedic Surgery The Affiliated Hospital of Qingdao UniversityQingdaoShandong266061PR China Department of Laboratory Diagnostic Medicine Chongqing General HospitalChongqing400021PR China Institute of Bone and Joint Research and the Department of Orthopaedic SurgeryThe Second Hospitals of Lanzhou UniversityGansuLanzhou730030PR China Department of Orthopaedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430072PR China Department of Spine Surgery Second Xiangya HospitalCentral South UniversityChangshaHunan410011PR China

Notch is a cellecell signaling pathway that is involved in a host of activities including development,oncogenesis,skeletal homeostasis,and much *** specifically,recent research has demonstrated the importance of Notch signaling in osteogenic differentiation,bone healing,and in the development of the *** craniofacial skeleton is complex and understanding its development has remained an important focus in *** this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton,skull,and face *** then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system,and what importance it may play in the future.

关键词： Alagille syndrome Bone Craniofacial development Craniosynostosis Notch Oncogenesis Osteogenesis Spondylocostal dysosotosis