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A maternal brain hormone that builds bone.
Babey, Muriel E; Krause, William C; Chen, Kun; Herber, Candice B; Torok, Zsofia; Nikkanen, Joni; Rodriguez, Ruben; Zhang, Xiao; Castro-Navarro, Fernanda; Wang, Yuting; Wheeler, Erika E; Villeda, Saul; Leach, J Kent; Lane, Nancy E; Scheller, Erica L; Chan, Charles K F; Ambrosi, Thomas H; Ingraham, Holly A.
Affiliation
  • Babey ME; Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Francisco, San Francisco, CA, USA.
  • Krause WC; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
  • Chen K; Department of Orthopaedic Surgery, University of California, Davis, Sacramento, CA, USA.
  • Herber CB; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
  • Torok Z; Denali Therapeutics, South San Francisco, CA, USA.
  • Nikkanen J; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
  • Rodriguez R; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
  • Zhang X; Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, USA.
  • Castro-Navarro F; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
  • Wang Y; Carmot Therapeutics, Berkeley, CA, USA.
  • Wheeler EE; Department of Medicine, Washington University, St Louis, MO, USA.
  • Villeda S; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
  • Leach JK; Institute for Stem Cell Biology and Regenerative Medicine and Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Lane NE; Department of Orthopaedic Surgery, University of California, Davis, Sacramento, CA, USA.
  • Scheller EL; Department of Biomedical Engineering, University of California, Davis, Davis, CA, USA.
  • Chan CKF; Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA.
  • Ambrosi TH; Department of Orthopaedic Surgery, University of California, Davis, Sacramento, CA, USA.
  • Ingraham HA; Department of Biomedical Engineering, University of California, Davis, Davis, CA, USA.
Nature ; 632(8024): 357-365, 2024 Aug.
Article in En | MEDLINE | ID: mdl-38987585
ABSTRACT
In lactating mothers, the high calcium (Ca2+) demand for milk production triggers significant bone loss1. Although oestrogen normally counteracts excessive bone resorption by promoting bone formation, this sex steroid drops precipitously during this postpartum period. Here we report that brain-derived cellular communication network factor 3 (CCN3) secreted from KISS1 neurons of the arcuate nucleus (ARCKISS1) fills this void and functions as a potent osteoanabolic factor to build bone in lactating females. We began by showing that our previously reported female-specific, dense bone phenotype2 originates from a humoral factor that promotes bone mass and acts on skeletal stem cells to increase their frequency and osteochondrogenic potential. This circulatory factor was then identified as CCN3, a brain-derived hormone from ARCKISS1 neurons that is able to stimulate mouse and human skeletal stem cell activity, increase bone remodelling and accelerate fracture repair in young and old mice of both sexes. The role of CCN3 in normal female physiology was revealed after detecting a burst of CCN3 expression in ARCKISS1 neurons coincident with lactation. After reducing CCN3 in ARCKISS1 neurons, lactating mothers lost bone and failed to sustain their progeny when challenged with a low-calcium diet. Our findings establish CCN3 as a potentially new therapeutic osteoanabolic hormone for both sexes and define a new maternal brain hormone for ensuring species survival in mammals.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteogenesis / Bone and Bones / Brain / Bone Density / Nephroblastoma Overexpressed Protein / Hormones / Mothers Limits: Adolescent / Animals / Female / Humans / Male Language: En Journal: Nature Year: 2024 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Osteogenesis / Bone and Bones / Brain / Bone Density / Nephroblastoma Overexpressed Protein / Hormones / Mothers Limits: Adolescent / Animals / Female / Humans / Male Language: En Journal: Nature Year: 2024 Document type: Article