PUBLICATION
The endocannabinoid system and retinoic acid signaling combine to influence bone growth
- Authors
- Fraher, D., Mann, R.J., Dubuisson, M.J., Ellis, M.K., Yu, T., Walder, K., Ward, A.C., Winkler, C., Gibert, Y.
- ID
- ZDB-PUB-210413-4
- Date
- 2021
- Source
- Molecular and Cellular Endocrinology 529: 111267 (Journal)
- Registered Authors
- Gibert, Yann, Winkler, Christoph
- Keywords
- Retinoic acid, endocannabinoid, medaka, osteoblast, osteoclast, zebrafish
- 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
- PubMed
- 33839219 Full text @ Mol. Cell. Endocrinol.
Citation
Fraher, D., Mann, R.J., Dubuisson, M.J., Ellis, M.K., Yu, T., Walder, K., Ward, A.C., Winkler, C., Gibert, Y. (2021) The endocannabinoid system and retinoic acid signaling combine to influence bone growth. Molecular and Cellular Endocrinology. 529:111267.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping