PUBLICATION
Longan fruit increase bone mineral density in zebrafish and ovariectomized rat by suppressing RANKL-induced osteoclast differentiation
- Authors
- Son, Y., Lee, E.M., Lee, D.Y., Lee, J.H., Oh, S.
- ID
- ZDB-PUB-190413-14
- Date
- 2019
- Source
- Phytomedicine : international journal of phytotherapy and phytopharmacology 59: 152910 (Journal)
- Registered Authors
- Keywords
- Bone mineral density, Longan fruit extract, NF-κB, Osteoclast differentiation, RANKL
- MeSH Terms
-
- Animals
- Bone Density/drug effects*
- Bone Resorption/drug therapy
- Cathepsin K/metabolism
- Cell Differentiation/drug effects*
- Down-Regulation/drug effects
- Fruit*
- Mice
- NF-kappa B/metabolism
- Osteoclasts/drug effects*
- Osteoclasts/physiology
- Osteoporosis/prevention & control
- Proto-Oncogene Proteins c-fos/metabolism
- RANK Ligand/metabolism*
- RAW 264.7 Cells
- Rats
- Signal Transduction/drug effects
- Zebrafish/metabolism
- PubMed
- 30978650 Full text @ Phytomedicine
Citation
Son, Y., Lee, E.M., Lee, D.Y., Lee, J.H., Oh, S. (2019) Longan fruit increase bone mineral density in zebrafish and ovariectomized rat by suppressing RANKL-induced osteoclast differentiation. Phytomedicine : international journal of phytotherapy and phytopharmacology. 59:152910.
Abstract
Background The receptor activator of nuclear factor-kappa B ligand (RANKL)-induced nuclear factor-kappa B (NF-κB) signaling pathway plays essential roles in osteoclast differentiation and may serve as an attractive target for the development of therapeutics for osteoporosis.
Purpose This study aimed to identify plant extracts that attenuated RANKL-induced NF-κB signaling pathway and examine their anti-osteoporotic effects in animal model systems.
Methods Osteoclast differentiation was determined by western blot analysis, RT-PCR, and tartrate-resistant acid phosphatase (TRAP) assay. The effect of Longan (Dimocarpus longan Lour.) fruit extract (LFE) on bone mineral density was evaluated by calcein staining in zebrafish and micro-CT analysis in ovariectomized (OVX) rat.
Results LFE nullified RANKL-induced down-regulation of inhibitor of NF-κB, which keeps NF-κB sequestered in the cytosol, thereby inhibiting translocation of NF-κB to the nucleus, in RAW264.7 cells. In addition, LFE decreased the nuclear levels of c-Fos and nuclear factor of activated T-cells c1, which play crucial roles in RANKL-induced osteoclast differentiation, in RAW264.7 cells. LFE repressed RANKL-activated cathepsin K and TRAP expression in RAW264.7 cells, resulting in a reduction of the number of TRAP-positive multinucleated cells, without cytotoxicity. Furthermore, LFE increased bone mineralization in zebrafish and prevented bone loss in OVX rat.
Conclusion Collectively, our findings suggest that LFE exerts its anti-osteoporotic activity through inhibition of osteoclast differentiation and may have potential as a herbal therapeutic or preventive agent for the treatment of osteoporosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping