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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

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Assessing the academic achievement of United States orthopaedic departments

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World Journal of Orthopedics 2022年第2期13卷 201-211页

作者： Rishi Trikha Thomas E Olson Ameen Chaudry Chad R Ishmael Cristina Villalpando Clark J Chen Kellyn R Hori Nicholas M Bernthal Department of orthopaedic surgery University of CaliforniaLos AngelesCA 90404United States Department of orthopaedic surgery David Geffen School of Medicine at UCLALos AngelesCA 90095United States

BACKGROUND Assessing academic productivity allows academic departments to identify the strengths of their scholarly contribution and provides an opportunity to evaluate areas for *** To provide objective benchmarks for departments seeking to enhance academic productivity and identify those with significant improvement in recent *** Our study retrospectively analyzed a cohort of orthopaedic faculty at United States-based academic orthopaedic programs.5502 full-time orthopaedic faculty representing 178 programs were included in *** included for analysis were National Institutes of Health funding(2014-2018),leadership positions in orthopaedic societies(2018),editorial board positions of top orthopaedic journals(2018),total number of publications and Hirsch-index.A weighted algorithm was used to calculate a cumulative score for each academic *** study was performed at a large,United States medical *** All 178 programs included in analysis were evaluated using the comprehensive weighted *** five institutions with the highest cumulative score,in decreasing order,were:Washington University in ***,the Hospital for Special surgery,Sidney Kimmel Medical College(SKMC)at Thomas Jefferson University,the University of California,San Francisco(UCSF)and Massachusetts General Hospital(MGH)/Brigham and Women’s/*** five institutions with the highest score per capita,in decreasing order,were:Mayo Clinic(Rochester),Washington University in ***,Rush University,Virginia Commonwealth University(VCU)and MGH/Brigham and Women’s/*** five academic programs that had the largest improvement in cumulative score from 2013 to 2018,in decreasing order,were:VCU,SKMC at Thomas Jefferson University,UCSF,MGH/Brigham and Women’s/Harvard,and Brown *** This algorithm can provide orthopaedic departments a means to assess academic productivity,monitor progress,and identify areas for improvement as th

关键词： Bibliometrics Academic achievement Number of publications National Institutes of Health funding Hirsch-index

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Histone demethylase Kdm5c regulates osteogenesis and bone formation via PI3K/Akt/HIF1α and Wnt/β-catenin signaling pathways

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Genes & Diseases 2024年第1期11卷 64-66页

作者： Ying Li Lingli Ding Yage Zhang Bingyu Zhou Gene Chi Wai Man Min Wang Jinglan Li Yamei Liu Weiping Lin Haibin Wang Sien Lin Liangliang Xu Key Laboratory of orthopaedics&Traumatology Lingnan Medical Research CenterThe First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou University of Chinese MedicineGuangzhouGuangdong 510000China Department of orthopaedics&Traumatology Faculty of MedicineThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong SAR 999077China departments of Diagnostics of Traditional Chinese Medicine Guangzhou University of Chinese MedicineGuangzhouGuangdong 510000China orthopaedic Research Lab Affiliated Hospital of Guangdong Medical UniversityGuangdong Medical UniversityZhanjiangGuangdong 524001China

Fractures have an extraordinarily negative impact on individuals'quality of life and functional *** or disability of fracture is a major health issue with important clinical,social,and economic implications.1 Mesenchymal stem cells(MSCs)play an indispensable role in the initiation of the fracture repair process including the formation of a callus which is replaced by new *** use of MSCs in the treatment of fractures is very attractive as they can reduce the time of healing and occurrence of nonunion.

关键词： PI3K/Akt HIF1α healing

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Kartogenin induces cartilage-like tissue formation in tendon–bone junction

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Bone Research 2014年第1期2卷 61-70页

作者： Jianying Zhang James H-C Wang MechanoBiology Laboratory Departments of Orthopaedic Surgery Bioengineering Mechanical Engineering and Materials Science and Physical Medicine and Rehabilitation University of Pittsburgh

Tendon-bone junctions （TBJs） are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin （KGN）, a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells （BMSCs） and patellar tendon stern/progenitor cells （PTSCs） in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs.

关键词： bone junction BMSCs

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Highly expressed BMP9/GDF2 in postnatal mouse liver and lungs may account for its pleiotropic effects on stem cell differentiation,angiogenesis,tumor growth and metabolism

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Genes & Diseases 2020年第2期7卷 235-244页

作者： Wei Liu Zhongliang Deng Zongyue Zeng Jiaming Fan Yixiao Feng Xi Wang Daigui Cao Bo Zhang Lijuan Yang Bin Liu Mikhail Pakvasa William Wagstaff Xiaoxing Wu Huaxiu Luo Jing Zhang Meng Zhang Fang He Yukun Mao Huiming Ding Yongtao Zhang Changchun Niu Rex C.Haydon Hue H.Luu Jennifer Moriatis Wolf Michael J.Lee Wei Huang Tong-Chuan He Yulong Zou departments of Orthopedic surgery Breast SurgeryGastrointestinal SurgeryObstetrics and Gynecologyand NephrologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of orthopaedic surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Ministry of Education Key Laboratory of Diagnostic Medicine The School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China departments of orthopaedic surgery and Laboratory Diagnostic Medicine Chongqing General HospitalChongqing 400021China Key Laboratory of orthopaedic surgery of Gansu Province The Departments of Orthopaedic Surgery and Obstetrics and GynecologyThe First and Second Hospitals of Lanzhou UniversityLanzhou730030China School of Life Sciences Southwest UniversityChongqing 400715China Department of Burn and Plastic surgery West China Hospital of Sichuan UniversityChengdu 610041China Department of orthopaedic surgery The First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405China Department of orthopaedic surgery The Affiliated Zhongnan Hospital of Wuhan UniversityWuhan 430072China Department of orthopaedic surgery BenQ Medical Center Affiliated with Nanjing Medical UniversityNanjing 210000China Department of orthopaedic surgery The Affiliated Hospital of Qingdao UniversityQingdao 266061China

Bone morphogenetic protein 9(BMP9)(or GDF2)was originally identified from fetal mouse liver cDNA *** evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in maintaining tissue ***,the expression landscape of BMP9 signaling during development and/or in adult tissues remains to be ***,we conducted a comprehensive analysis of the expression landscape of BMP9 and its signaling mediators in postnatal *** analyzing mouse ENCODE transcriptome datasets we found Bmp9 was highly expressed in the liver and detectable in embryonic brain,adult lungs and adult *** next conducted a comprehensive qPCR analysis of RNAs isolated from major mouse tissues/organs at various *** found that Bmp9 was highly expressed in the liver and lung tissues of young adult mice,but decreased in older ***,Bmp9 was only expressed at low to modest levels in developing ***9-associated TGFβ/BMPR type I receptor Alk1 was highly expressed in the adult ***,the feedback inhibitor Smads Smad6 and Smad7 were widely expressed in mouse postnatal ***,the BMP signaling antagonist noggin was highly expressed in fat and heart in the older age groups,as well as in kidney,liver and lungs in a biphasic ***,our findings indicate that the circulating BMP9 produced in liver and lungs may account for its pleiotropic effects on postnatal tissues/organs although possible roles of BMP9 signaling in liver and lungs remain to be fully understood.

关键词： BMP9/GDF2 Bone morphogenetic proteins(BMPs) Hepatic metabolism Mesenchymal stem cells Neurogenesis Osteogenic differentiation Pulmonary arterial hypertension Tumorigenesis

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Sacroiliac joint stability: Finite element analysis of implant number, orientation, and superior implant length

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World Journal of Orthopedics 2018年第3期9卷 14-23页

作者： Derek P Lindsey Ali Kiapour Scott A Yerby Vijay K Goel Research and Development SI-BONE Inc. Engineering Center for orthopaedic Research Excellence Departments of Bioengineering and Orthopaedic Surgery Colleges of Engineering and MedicineUniversity of Toledo

AIM To analyze how various implants placement variables affect sacroiliac(SI) joint range of motion. METHODS An experimentally validated finite element model of the lumbar spine and pelvis was used to simulate a fusion of the SI joint using various placement configurations of triangular implants(iF use Implant System~?). Placement configurations were varied by changing implant orientation, superior implant length, and number of implants. The range of motion of the SI joint was calculated using a constant moment of 10 N-m with a follower load of 400 N. The changes in motion were compared between the treatment groups to assess how the different variables affected the overall motion of the SI joint. RESULTS Transarticular placement of 3 implants with superior implants that end in the middle of the sacrum resulted in the greatest reduction in range of motion(flexion/extension = 73%, lateral bending = 42%, axial rotation = 72%). The range of motions of the SI joints were reduced with use of transarticular orientation(9%-18%) when compared with an inline orientation. The use of a superior implant that ended mid-sacrum resulted in median reductions of(8%-14%) when compared with a superior implant that ended in the middle of the ala. Reducing the number of implants, resulted in increased SI joint range of motions for the 1 and 2 implant models of 29%-133% and 2%-39%, respectively,when compared with the 3 implant *** Using a validated finite element model we demonstrated that placement of 3 implants across the SI joint using a transarticular orientation with superior implant reaching the sacral midline resulted in the most stable construct. Additional clinical studies may be required to confirm these results.

关键词： Fusion Biomechanics Minimally invasive surgery Sacroiliac joint dysfunction Finite element analysis

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Comparison of skeletal and soft tissue pericytes identifies CXCR4+ bone forming mural cells in human tissues

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Bone Research 2020年第3期8卷 286-299页

作者： Jiajia Xu Dongqing Li Ching-Yun Hsu Ye Tian Leititia Zhang Yiyun Wang Robert J.Tower Leslie Chang Carolyn A.Meyers Yongxing Gao Kristen Broderick Carol Morris Jody E.Hooper Sridhar Nimmagadda Bruno Peault Aaron W.James departments of Pathology Johns Hopkins UniversityBaltimore 21205 MDUSA Department of Microbiology Wuhan University School of Basic Medical of ScienceWuhanHubeiP.R.China Department of Oral and Maxillofacial surgery School of StomatologyChina Medical UniversityShenyangLiaoningP.R.China departments of orthopaedics Johns Hopkins UniversityBaltimore 21205 MDUSA departments of Plastic surgery Johns Hopkins UniversityBaltimore 21205 MDUSA departments of Autopsy Service Johns Hopkins UniversityBaltimoreMD 21205USA departments of Radiology and Radiological Science bonBaltimore 21205 MDUSA UCLA and orthopaedic Hospital Department of orthopaedic surgery and the orthopaedic Hospital Research Center Los AngelesCA 90095USA Center for Cardiovascular Science and MRC Center for Regenerative Medicine University of EdinburghEdinburghUK

Human osteogenic progenitors are not precisely defined,being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells(MSCs).Notably,select human pericytes can develop into bone-forming ***,we sought to define the differentiation potential of CD146 f human pericytes from skeletal and soft tissue sources,with the underlying goal of defining cell surface markers that typify an osteoblastogenic ***146+CD31~CD45_pericytes were derived by fluorescence-activated cell sorting from human periosteum,adipose,or dermal *** CD146+CD31—CD45 cells retained canonical features of pericytes/*** pericytes demonstrated a striking tendency to undergo osteoblastogenesis in vitro and skeletogenesis in vivo,while soft tissue pericytes did not *** analysis revealed higher CXCR4 signaling among periosteal pericytes in comparison to their soft tissue counterparts,and CXCR4 chemical inhibition abrogated ectopic ossification by periosteal ***,enrichment of CXCR4+pericytes or stromal cells identified an osteoblastic/non-adipocytic precursor *** sum,human skeletal and soft tissue pericytes differ in their basal abilities to form *** exists in soft tissue pericytes,however,and CXCR4+pericytes represent an osteoblastogenic,non-adipocytic cell ***,enrichment for CXCR4-expressing stromal cells is a potential new tactic for skeletal tissue engineering.

关键词： CD146 CXCR4 pericyte

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The versatile functions of Sox9 in development,stem cells,and human diseases

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Genes & Diseases 2014年第2期1卷 149-161页

作者： Alice Jo Sahitya Denduluri Bosi Zhang Zhongliang Wang Liangjun Yin Zhengjian Yan Richard Kang Lewis L.Shi James Mok Michael J.Lee Rex C.Haydon Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA departments of orthopaedic surgery The Affiliated Hospitals of Chongqing Medical UniversityChongqing 400046China

The transcription factor Sox9 was first discovered in patients with campomelic dysplasia,a haploinsufficiency disorder with skeletal deformities caused by dysregulation of Sox9 expression during *** then,its role as a cell fate determiner during embryonic development has been well characterized;Sox9 expression differentiates cells derived from all three germ layers into a large variety of specialized tissues and ***,recent data has shown that ectoderm-and endoderm-derived tissues continue to express Sox9 in mature organs and stem cell pools,suggesting its role in cell maintenance and specification during adult *** versatility of Sox9 may be explained by a combination of posttranscriptional modifications,binding partners,and the tissue type in which it is *** its importance during both development and adult life,it follows that dysregulation of Sox9 has been implicated in various congenital and acquired diseases,including fibrosis and *** review provides a summary of the various roles of Sox9 in cell fate specification,stem cell biology,and related human ***,understanding the mechanisms that regulate Sox9 will be crucial for developing effective therapies to treat disease caused by stem cell dysregulation or even reverse organ damage.

关键词： Development Sox9 Stem cells Transcription factor

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Establishment and functional characterization of the reversibly immortalized mouse glomerular podocytes(imPODs)

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Genes & Diseases 2018年第2期5卷 137-149页

作者： Xinyi Yu Liqun Chen Ke Wu Shujuan Yan Ruyi Zhang Chen Zhao Zongyue Zeng Yi Shu Shifeng Huang Jiayan Lei Xiaojuan Ji Chengfu Yuan Linghuan Zhang Yixiao Feng Wei Liu Bo Huang Bo Zhang Wenping Luo Xi Wang Bo Liu Rex C.Haydon Hue H.Luu Tong-Chuan He Hua Gan departments of Nephrology Orthopaedic SurgeryCardiologyGeneral SurgeryPlastic Surgeryand Clinical Laboratory MedicineThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine and the Affiliated Hospitals of Chongqing Medical UniversityChongqing400016China Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichang443002China Department of Clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang330031China Key Laboratory of orthopaedic surgery of Gansu Province and the Department of orthopaedic surgery The Second Hospital of Lanzhou UniversityLanzhou730030China

Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of *** the viability and structural integrity of podocytes is critical to the clinical management of glomerular diseases,which requires a thorough understanding of podocyte cell *** mature podocytes lose proliferative capacity,a conditionally SV40 mutant tsA58-immortalized mouse podocyte line(designated as tsPC)was established from the Immortomouse over 20 years ***,the utility of the tsPC cells is hampered by the practical inconvenience of culturing these *** this study,we establish a user-friendly and reversibly-immortalized mouse podocyte line(designated as imPOD),on the basis of the tsPC cells by stably expressing the wildtype SV40 T-antigen,which is flanked with FRT *** show the imPOD cells exhibit long-term high proliferative activity,which can be effectively reversed by FLP *** imPOD cells express most podocyte-related markers,including WT-1,Nephrin,Tubulin and Vinculin,but not differentiation marker *** imPOD cells do not form tumor-like masses in *** further demonstrate that TGFb1 induces a podocyte injury-like response in the FLP-reverted imPOD cells by suppressing the expression of slit diaphragm-associated proteins P-Cadherin and ZO-1 and upregulating the expression of mesenchymal markers,a-SMA,Vimentin and Nestin,as well as fibrogenic factors CTGF and ***,our results strongly demonstrate that the newly engineered im-POD cells should be a valuable tool to study podocyte biology both under normal and under pathological conditions.

关键词： Chronic kidney disease FLP recombinase Glomerular disease Glomerulus Immortalization Nephropathy Podocyte SV40 T antigen

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Isolated Metastatic Barrett’s Adenocarcinoma of the Thoracic Epidural Space Causing Paraplegia

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Open Journal of Orthopedics 2013年第1期3卷 1-3页

作者： Tomohiro Banno Tsuyoshi Ohishi Daisuke Suzuki Kazufumi Yamamoto Hiroki Ushirozako Sho Kobayashi Yukihiro Matsuyama departments of orthopaedic surgery Enshu Hospital Hamamatsu Shizuoka Japan departments of orthopaedic surgery Hama- matsu University School of Medicine Hamamatsu Shizuoka Japan. departments of orthopaedic surgery Hamamatsu University School of Medicine Hamamatsu Shizuoka Japan.

Barrett’s adenocarcinoma is an esophageal cancer arising from Barrett’s esophagus. In this report, a metastatic epidural tumor from Barrett’s adenocarcinoma with paraplegia that required surgical treatment is documented. A 50-year-old man who had had a resection of the distal esophagus due to Barrett’s adenocarcinoma six month before presented with progressive weakness and numbness in lower limbs with urinary disturbance. Magnetic resonance imaging of the thoracic region revealed compression of the spinal cord at the T3-4 level by a dorsally located epidural mass. No signal changes were detected in vertebrae. Since the paraplegia and urinary disturbance were rapidly progressing, laminectomy and tumor resection was performed. Postoperatively, neurological function improved immediately and there was no recurrence of spinal region. This is the first report on an isolated metastatic Barrett’s adenocarcinoma of the thoracic epidural space.

关键词： Barrett’s Adenocarcinoma Metastasis Isolated Epidural Tumor

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