title: Osteocrin, a peptide secreted from the heart and other tissues, contributes to cranial osteogenesis and chondrogenesis in zebrafish.
abstract: The heart is an endocrine organ, as cardiomyocytes (CMs) secrete natriuretic peptide (NP) hormones. Since the discovery of NPs, no other peptide hormones that affect remote organs have been identified from the heart. We identified osteocrin (Ostn) as an osteogenesis/chondrogenesis regulatory hormone secreted from CMs in zebrafish. ostn mutant larvae exhibit impaired membranous and chondral bone formation. The impaired bones were recovered by CM-specific overexpression of OSTN. We analyzed the parasphenoid (ps) as a representative of membranous bones. In the shortened ps of ostn morphants, nuclear Yap1/Wwtr1-dependent transcription was increased, suggesting that Ostn might induce the nuclear export of Yap1/Wwtr1 in osteoblasts. Although OSTN is proposed to bind to NPR3 (clearance receptor for NPs) to enhance the binding of NPs to NPR1 or NPR2, OSTN enhanced C-type NP (CNP)-dependent nuclear export of YAP1/WWTR1 of cultured mouse osteoblasts stimulated with saturable CNP. OSTN might therefore activate unidentified receptors that augment protein kinase G signaling mediated by a CNP-NPR2 signaling axis. These data demonstrate that Ostn secreted from the heart contributes to bone formation as an endocrine hormone.
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Ayano
authors.initials: A
authors.lastname: Chiba
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Watanabe-Takano
authors.affiliation: Laboratory of Function and Morphology, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Terai
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Fukui
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Laboratory of Function and Morphology, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Uemura
authors.affiliation: Laboratory of Organogenesis and Organ Function, Bioscience and Biotechnology Center, Nagoya University, Furo-cho, Chigusa-ku, Nagoya, Aichi 464-8061, Japan.|Devision of Biological Science, Graduate School of Science Nagoya, Nagoya University, Furo-cho, Chigusa-ku, Nagoya, Aichi 464-8061, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Laboratory of Organogenesis and Organ Function, Bioscience and Biotechnology Center, Nagoya University, Furo-cho, Chigusa-ku, Nagoya, Aichi 464-8061, Japan.|Devision of Biological Science, Graduate School of Science Nagoya, Nagoya University, Furo-cho, Chigusa-ku, Nagoya, Aichi 464-8061, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hibi
authors.affiliation: Department of Molecular Pathophysiology, Institute of Advanced Medical Science, Nippon Medical School, 1-396 Kosugi-machi, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan.
authors.forename: Shigetomo
authors.initials: S
authors.lastname: Fukuhara
authors.affiliation: Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan nmochizu@ri.ncvc.go.jp.|AMED-CREST, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Naoki
authors.identifier: 0000-0002-3938-9602
authors.initials: N
authors.lastname: Mochizuki
mesh_terms: D000825:Animal Structures / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics*; D004625:Embryo, Nonmammalian; D057809:HEK293 Cells; D006321:Heart / Q000378:metabolism; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D038081:Organogenesis / Q000187:drug effects / Q000235:genetics; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D012886:Skull / Q000187:drug effects / Q000196:embryology*; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
chemical_list: D036361:Peptide Hormones; D014157:Transcription Factors; D029961:Zebrafish Proteins; C000622819:osteocrin, zebrafish
keywords: Chondrogenesis; Heart; Nppa; Nppb; Nppc; Osteocrin; Osteogenesis; Peptide