The endocannabinoid system and retinoic acid signaling combine to influence bone growth

Mol Cell Endocrinol. 2021 Jun 1:529:111267. doi: 10.1016/j.mce.2021.111267. Epub 2021 Apr 9.

Abstract

Osteoporosis is an increasing burden on public health as the world-wide population ages and effective therapeutics are severely needed. Two pathways with high potential for osteoporosis treatment are the retinoic acid (RA) and endocannabinoid system (ECS) signaling pathways. We sought to elucidate the roles that these pathways play in bone development and maturation. Here, we use chemical treatments to modulate the RA and ECS pathways at distinct early, intermediate, and late times bone development in zebrafish. We further assessed osteoclast activity later in zebrafish and medaka. Finally, by combining sub-optimal doses of AR and ECS modulators, we show that enhancing RA signaling or reducing the ECS promote bone formation and decrease osteoclast abundance and activity. These data demonstrate that RA signaling and the ECS can be combined as sub-optimal doses to influence bone growth and may be key targets for potential therapeutics.

Keywords: Endocannabinoid; Medaka; Osteoblast; Osteoclast; Retinoic acid; Zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Development / drug effects
  • Bone Development / genetics
  • Embryo, Nonmammalian
  • Endocannabinoids / metabolism*
  • Gene Expression Regulation, Developmental
  • Oryzias / genetics*
  • Oryzias / growth & development
  • Oryzias / metabolism
  • Osteoclasts / cytology
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects
  • Osteogenesis / genetics
  • Osteonectin / genetics
  • Osteonectin / metabolism
  • Rimonabant / pharmacology
  • Signal Transduction / genetics*
  • Sp7 Transcription Factor / genetics
  • Sp7 Transcription Factor / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Tretinoin / metabolism*
  • Tretinoin / pharmacology
  • Zebrafish / genetics*
  • Zebrafish / growth & development
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism

Substances

  • Endocannabinoids
  • Osteonectin
  • Runx2a protein, zebrafish
  • Runx2b protein, zebrafish
  • Sp7 Transcription Factor
  • Transcription Factors
  • Zebrafish Proteins
  • sp7 protein, zebrafish
  • Tretinoin
  • Rimonabant