ArticleNature communications2024
Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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11 citing papers in PubMed, 14 citations in OpenAlex.
- Sulfated polysaccharides target RANK Lys97 to inhibit osteoclast differentiation and reverse osteoporosis.Nature biomedical engineering · 2026Article
- NanoBRET-based detection of ligand-receptor interactions at the neuropeptide FF receptor 1.RSC advances · 2026Article
- Hyperoside Modulates the Estrogen-PI3K/VEGF Axis to Ameliorate Oxidative Damage-Induced Inhibition of Bone Formation in MC3T3-E1 Cells.Immunity, inflammation and disease · 2026Article
- Cellular and molecular mechanisms of seahorse male pregnancy.Nature ecology & evolution · 2025Article
- Oral Engineered Extracellular Vesicles Based on Ion Exchange Strategy for Multipronged Management of Wilson's Disease Complicated with Reproductive Dysfunction Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ICAM-1-mediated Src signaling pathway plays a pivotal role in encephalomyocarditis virus entry.Journal of virology · 2025Article
- Hypothalamic kisspeptin alleviates myasthenia gravis by regulating Th1/Th17/Treg balance through Inhibition of NF-κB signaling pathway.Journal of neuroinflammation · 2025Article
- Kisspeptin and neurokinin B: roles in reproductive health.Physiological reviews · 2025Review
- Application of integrated omics in aseptic loosening of prostheses after hip replacement.Molecular medicine reports · 2025Article
- The function of GPCRs in different bone cells.International journal of biological sciences · 2025Review
- Beyond resorption: osteoclasts as drivers of bone formation.Cell regeneration (London, England) · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
32 authors at 8 institutions in 2 countries.
Zhenxi Li *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.ORCID 0000-0002-7220-6177
Xinghai Yang *Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Ruifeng Fu *Institute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
Zhipeng Wu *Institute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Shengzhao XuEast 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.
Jian JiaoInstitute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Ming QianInstitute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Long ZhangInstitute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
Chunbiao WuInstitute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
Tianying XieInstitute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
Jiqiang YaoInstitute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Zhixiang WuInstitute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Wenjun LiEast 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.
Guoli MaEast 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.
Yu YouEast 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.ORCID 0000-0002-0345-6201
Yihua ChenEast 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.ORCID 0000-0003-1733-7980
Han-Kun ZhangEast 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.
Yiyun ChengEast 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.
Xiaolong TangSchool of Biomedical Sciences, Hunan University, Changsha, 410082, China.ORCID 0000-0002-4744-5846
Pengfei WuDepartment of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.ORCID 0000-0001-8297-3380
Gewei LianDepartment of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
Haifeng WeiInstitute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Jian ZhaoInstitute of Orthopedics, Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Jianrong XuAcademy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.ORCID 0000-0002-2168-2296
Lianzhong AiInstitute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
Stefan SiwkoDepartment of Translational Medical Sciences, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
Yue WangShanghai Key Lab of Cell Engineering; Translational Medicine Research Center, Naval Medical University, Shanghai, 200433, China.
Jin DingClinical Cancer Institute, Center for Translational Medicine, Naval Medical University, Shanghai, 200433, China.
Gaojie SongEast 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. gjsong@bio.ecnu.edu.cn.ORCID 0000-0002-7787-6452
Jian LuoYangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, China. jluo@tongji.edu.cn.ORCID 0000-0003-3583-0154
Mingyao LiuEast 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. myliu@bio.ecnu.edu.cn.ORCID 0000-0001-7339-5048
Jianru XiaoInstitute of Orthopedic Biomedical and Device Innovation, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China. jianruxiao83@163.com.
Shanghai Changzheng Hospital · CNUniversity of Shanghai for Science and Technology · CNBeth Israel Deaconess Medical Center · USHunan University · CNShanghai Cell Therapy Research Institute · CNShanghai Sunshine Rehabilitation Center · CNShanghai University of Traditional Chinese Medicine · CNTexas A&M University · US
Funding
Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 22PJ1416000
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.
Indexed as
Bone ResorptionOsteoclastsAnimalsKisspeptinsMiceMice, KnockoutReceptors, G-Protein-CoupledReceptors, Kisspeptin-1src-Family KinasesKISS1 protein, humanKisspeptinsReceptors, G-Protein-CoupledReceptors, Kisspeptin-1src-Family Kinases
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.