title: Regulation of bone formation by baicalein via the mTORC1 pathway.
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.
authors.affiliation: Academy of Orthopedics of Guangdong Province, Guangzhou, People's Republic of China ; Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Sheng-fa
authors.initials: SF
authors.lastname: Li
authors.affiliation: Academy of Orthopedics of Guangdong Province, Guangzhou, People's Republic of China ; Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jia-jun
authors.initials: JJ
authors.lastname: Tang
authors.affiliation: Academy of Orthopedics of Guangdong Province, Guangzhou, People's Republic of China ; Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China ; Three Gorges Central Hospital of Chongqing, Chongqing, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Academy of Orthopedics of Guangdong Province, Guangzhou, People's Republic of China ; Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Tian-yu
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Academy of Orthopedics of Guangdong Province, Guangzhou, People's Republic of China ; Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: Academy of Orthopedics of Guangdong Province, Guangzhou, People's Republic of China ; Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: Academy of Orthopedics of Guangdong Province, Guangzhou, People's Republic of China ; Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Academy of Orthopedics of Guangdong Province, Guangzhou, People's Republic of China ; Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Min-jun
authors.initials: MJ
authors.lastname: Huang
authors.affiliation: Academy of Orthopedics of Guangdong Province, Guangzhou, People's Republic of China ; Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zhong-min
authors.initials: ZM
authors.lastname: Zhang
authors.affiliation: Academy of Orthopedics of Guangdong Province, Guangzhou, People's Republic of China ; Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Da-di
authors.initials: DD
authors.lastname: Jin
mesh_terms: D000818:Animals; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D044950:Flavanones / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control; D010052:Ovariectomy; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D044950:Flavanones; D046912:Multiprotein Complexes; D015675:Osteocalcin; C006680:baicalein; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: mTOR; menopause; osteoblast; osteoporosis