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

作     者：Rexhina Vlashi Xingen Zhang Mengrui Wu Guiqian Chen Rexhina Vlashi;Xingen Zhang;Mengrui Wu;Guiqian Chen

作者机构：College of Life Science and MedicineZhejiang Provincial Key Laboratory of Silkworm Bioreactor and BiomedicineZhejiang Sci-Tech UniversityHangzhouZhejiang 310018China Department of OrthopedicsJiaxing Key Laboratory for Minimally Invasive Surgery in Orthopaedics&Skeletal Regenerative MedicineZhejiang Rongjun HospitalJiaxingZhejiang 314001China Institute of GeneticsCollege of Life ScienceZhejiang UniversityHangzhouZhejiang 310058China 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2023年第10卷第4期

页      面：1291-1317页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：supported by grants by Zhejiang Qianjiang Talent Program(No.21040040-E) the Department of Sci-Tech of Zhejiang Province(No.LGF19H140002) a startup grant from Zhejiang Sci-Tech University(No.18042290-Y,2021Q031) funds from National Natural Science Foundation of China(No.81900806,81400489) the basic Public Welfare Planning Project of Zhejiang Province(No.LGD20C040001) Jiaxing Science Technology Foundation(No.2020AY10001) Jiaxing Key Laboratory of Animal Model Generation and Precise Synthesis of New Drug Leads 

主　　题：Bone development Bone homeostasis Osteoblast differentiation Skeletal disorders Wnt signaling 

摘      要：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.