Osteocrin, a peptide secreted from the heart and other tissues, contributes to cranial osteogenesis and chondrogenesis in zebrafish

Development. 2017 Jan 15;144(2):334-344. doi: 10.1242/dev.143354. Epub 2016 Dec 19.

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.

Keywords: Chondrogenesis; Heart; Nppa; Nppb; Nppc; Osteocrin; Osteogenesis; Peptide.

MeSH terms

  • Animal Structures / metabolism
  • Animals
  • Animals, Genetically Modified
  • Cells, Cultured
  • Chondrogenesis / drug effects
  • Chondrogenesis / genetics*
  • Embryo, Nonmammalian
  • HEK293 Cells
  • Heart / metabolism
  • Humans
  • Mice
  • Myocytes, Cardiac / metabolism*
  • Organogenesis / drug effects
  • Organogenesis / genetics
  • Osteogenesis / drug effects
  • Osteogenesis / genetics*
  • Peptide Hormones / genetics
  • Peptide Hormones / metabolism
  • Peptide Hormones / pharmacology
  • Peptide Hormones / physiology
  • Skull / drug effects
  • Skull / embryology*
  • Transcription Factors / metabolism
  • Transcription Factors / pharmacology
  • Transcription Factors / physiology*
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / metabolism
  • Zebrafish Proteins / pharmacology
  • Zebrafish Proteins / physiology*

Substances

  • Peptide Hormones
  • Transcription Factors
  • Zebrafish Proteins
  • osteocrin, zebrafish