title: Isopsoralen-mediated suppression of bone marrow adiposity and attenuation of the adipogenic commitment of bone marrow-derived mesenchymal stem cells.
abstract: Osteoporosis (OP) increases the risk of bone fractures and other complications, and is thus a major clinical problem. In this study, we examined the effect of isopsoralen on the differentiation of bone-derived marrow mesenchymal stem cells (BMSCs) into osteoblasts and adipocytes, as well as bone formation under osteoporotic conditions. Primary femoral BMSCs isolated from C57BL/6 mice were used to evaluate the isopsoralen-mediated regulation of the expression of alkaline phosphatase (ALP), osteocalcin (OCN) and runt-related transcription factor 2 (RUNX2) during osteogenesis 2 weeks. We also examined the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein β (C/EBPβ) under adipogenic conditions for 1 and 2 weeks. In addition, ovariectomized (OVX) mice were used to examine the effects of isopsoralen on bone formation for 2 months. Finally, mammalian target of rapamycin complex 1 (mTORC1) signaling was examined under osteogenic and adipogenic conditions. We found that following treatment with isopsoralen, the expression levels of ALP, OCN and RUNX2 were upregulated, whereas those of PPARγ and C/EBPβ were downregulated. mTORC1 signaling was also inhibited in vitro and in vivo. In the OVX mice that were intragastrically administered isopsoralen, bone parameters (trabecular thickness, bone volume/total volume and trabecular number) in the distal femoral metaphysis were significantly increased and the adipocyte number was decreased. On the whole, our findings demonstrate that isopsoralen promoted BMSC differentiation into osteoblasts and suppressed differentiation into adipocytes.
authors.affiliation: Department of Orthopaedics, People's Hospital of Inner Mongolia Autonomous Region, Hohhot 010050, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The First People's Hospital of Huizhou, Huizhou, Guangdong 516003, P.R. China.
authors.forename: Sheng-Fa
authors.initials: SF
authors.lastname: Li
authors.affiliation: Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, The First People's Hospital of Huizhou, Huizhou, Guangdong 516003, P.R. China.
authors.forename: Chun-Han
authors.initials: CH
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Guangdong Orthopedics Academy, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510665, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Guangdong Orthopedics Academy, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510665, P.R. China.
authors.forename: Min-Jun
authors.initials: MJ
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, Three Gorges Central Hospital of Chongqing, Chongqing 404100, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, The First People's Hospital of Huizhou, Huizhou, Guangdong 516003, P.R. China.
authors.forename: Shao-Wei
authors.initials: SW
authors.lastname: Zheng
authors.affiliation: Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Medical Imaging, Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Guangdong Orthopedics Academy, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510665, P.R. China.
authors.forename: Tian-Yu
authors.initials: TY
authors.lastname: Chen
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D050154:Adiposity; D000818:Animals; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D011564:Furocoumarins / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015675:Osteocalcin / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D011564:Furocoumarins; D047495:PPAR gamma; D015675:Osteocalcin; C011659:angelicin