Your browser doesn't support javascript.
loading
Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src.
Li, Zhenxi; Yang, Xinghai; Fu, Ruifeng; Wu, Zhipeng; Xu, Shengzhao; Jiao, Jian; Qian, Ming; Zhang, Long; Wu, Chunbiao; Xie, Tianying; Yao, Jiqiang; Wu, Zhixiang; Li, Wenjun; Ma, Guoli; You, Yu; Chen, Yihua; Zhang, Han-Kun; Cheng, Yiyun; Tang, Xiaolong; Wu, Pengfei; Lian, Gewei; Wei, Haifeng; Zhao, Jian; Xu, Jianrong; Ai, Lianzhong; Siwko, Stefan; Wang, Yue; Ding, Jin; Song, Gaojie; Luo, Jian; Liu, Mingyao; Xiao, Jianru.
Afiliação
  • Li Z; Institute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China. zxli@usst.edu.cn.
  • Yang X; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China. zxli@usst.edu.cn.
  • Fu R; East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China. zxli@usst.edu.cn.
  • Wu Z; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. zxli@usst.edu.cn.
  • Xu S; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • Jiao J; Institute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
  • Qian M; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • Zhang L; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • Wu C; East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
  • Xie T; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • Yao J; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • Wu Z; Institute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
  • Li W; Institute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
  • Ma G; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • You Y; Institute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
  • Chen Y; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • Zhang HK; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • Cheng Y; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • Tang X; East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
  • Wu P; East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
  • Lian G; East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
  • Wei H; East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
  • Zhao J; East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
  • Xu J; East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
  • Ai L; School of Biomedical Sciences, Hunan University, Changsha, 410082, China.
  • Siwko S; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Wang Y; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
  • Ding J; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • Song G; Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
  • Luo J; Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Liu M; Institute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
  • Xiao J; Department of Translational Medical Sciences, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
Nat Commun ; 15(1): 1300, 2024 Feb 12.
Article em En | MEDLINE | ID: mdl-38346942
ABSTRACT
Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.
Assuntos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoclastos / Reabsorção Óssea Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoclastos / Reabsorção Óssea Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China