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Regulation of bone formation by baicalein via the mTORC1 pathway.
- Source :
-
Drug design, development and therapy [Drug Des Devel Ther] 2015 Sep 09; Vol. 9, pp. 5169-83. Date of Electronic Publication: 2015 Sep 09 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- Osteoporosis is a systemic skeletal disease that is characterized by low bone density and microarchitectural deterioration of bone tissue. The increasing prevalence of osteoporosis has attracted much attention. In this study, MC3T3-E1 pre-osteoblasts were treated with the natural compound, baicalein (0.1 μmol/L, 1 μmol/L, 10 μmol/L), to stimulate differentiation over a 14-day period. In addition, a canonical ovariectomized (OVX) mouse model was used to investigate the effect of 3-month baicalein treatment (10 mg/kg per day) in preventing postmenopausal osteoporosis. In vitro, we found that baicalein induced activation of alkaline phosphatase, stimulated the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, and induced expression of osteoblast differentiation markers, ie, osteocalcin, osterix, collagen Iα1, and runt-related transcription factor 2 (RUNX2), in osteoblasts. In vivo, several bone parameters, including trabecular thickness, trabecular bone mineral density, and trabecular number, in the distal femoral metaphysis were significantly increased in OVX mice treated intragastrically with baicalein for 3 months compared with OVX mice that were not treated with baicalein. We also found that expression of osteocalcin and RUNX2 was decreased in primary ossified tissue from the OVX group, and baicalein increased the levels of osteocalcin and RUNX2 in OVX mice. These data suggest that baicalein can stimulate MC3T3-E1 cells to differentiate into osteoblasts via activation of the mTORC1 signaling pathway, which includes protein kinases and transcription factors such as P-4E/BP1 and P-S6K1.
- Subjects :
- Animals
Cell Line
Core Binding Factor Alpha 1 Subunit metabolism
Dose-Response Relationship, Drug
Female
Flavanones administration & dosage
Humans
Mechanistic Target of Rapamycin Complex 1
Mice
Mice, Inbred C57BL
Osteoblasts metabolism
Osteocalcin metabolism
Osteoporosis, Postmenopausal prevention & control
Ovariectomy
Flavanones pharmacology
Multiprotein Complexes metabolism
Osteoblasts drug effects
Osteogenesis drug effects
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1177-8881
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Drug design, development and therapy
- Publication Type :
- Academic Journal
- Accession number :
- 26392752
- Full Text :
- https://doi.org/10.2147/DDDT.S81578