IRE1α regulates the PTHrP-IHH feedback loop to orchestrate chondrocyte hypertrophy and cartilage mineralization

作     者：Mengtian Fan Nana Geng Xingyue Li Danyang Yin Yuyou Yang Rong Jiang Cheng Chen Naibo Feng Li Liang Xiaoli Li Fengtao Luo Huabing Qi Qiaoyan Tan Yangli Xie Fengjin Guo Mengtian Fan;Nana Geng;Xingyue Li;Danyang Yin;Yuyou Yang;Rong Jiang;Cheng Chen;Naibo Feng;Li Liang;Xiaoli Li;Fengtao Luo;Huabing Qi;Qiaoyan Tan;Yangli Xie;Fengjin Guo

作者机构：Laboratory of Developmental BiologyDepartment of Cell Biology and GeneticsSchool of Basic Medical ScienceChongqing Medical UniversityChongqing 400016China Laboratory of Stem Cells and Tissue EngineeringSchool of Basic Medical ScienceChongqing Medical UniversityChongqing 400016China Department of OrthopedicsThe 1st Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Wound Repair and Rehabilitation MedicineState Key Laboratory of TraumaBurns and Combined InjuryTrauma CenterResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2024年第11卷第1期

页      面：464-478页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 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)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.81672209,81871769,82272550) the Chongqing Science and Technology Bureau(China)(No.cstc2021jcyj-bshX0214) 

主　　题：Cartilage development ER stress ERN1 IHH PTHrP/PTH1R 

摘      要：Cartilage development is controlled by the highly synergistic proliferation and differentiation of growth plate chondrocytes,in which the Indian hedgehog(IHH)and parathyroid hormone-related protein-parathyroid hormone-1 receptor(PTHrP-PTH1R)feedback loop is *** inositol-requiring enzyme 1a/X-box-binding protein-1 spliced(IRE1α/XBP1s)branch of the unfolded protein response(UPR)is essential for normal cartilage ***,the precise role of ER stress effector IRE1α,encoded by endoplasmic reticulum to nucleus signaling 1(ERN1),in skeletal development remains ***,we reported that loss of IRE1α accelerates chondrocyte hypertrophy and promotes endochondral bone ***1 acts as a negative regulator of chondrocyte proliferation and differentiation in postnatal growth *** deficiency interrupted PTHrP/PTH1R and IHH homeostasis leading to impaired chondrocyte hypertrophy and ***1s,produced by p-IRE1α-mediated splicing,binds and up-regulates PTH1R and IHH,which coordinate cartilage ***,ER stress cannot be activated normally in ERN1-deficient *** conclusion,ERN1 deficiency accelerates chondrocyte hypertrophy and cartilage mineralization by impairing the homeostasis of the IHH and PTHrP/PTH1R feedback loop and ER ***1 may have a potential role as a new target for cartilage growth and maturation.