title: Genistein induces adipogenic differentiation in human bone marrow mesenchymal stem cells and suppresses their osteogenic potential by upregulating PPARγ.
abstract: Genistein is a soy isoflavone that exists in the form of an aglycone. It is the primary active component in soy isoflavone and has a number of biological activities (anti-inflammatory and anti-oxidative). However, the specific effect of genistein on human bone marrow mesenchymal stem cells (BMSCs) remains unclear. In the present study, the mechanism underlying the effect of genistein on the suppression of BMSC adipogenic differentiation and the enhancement of osteogenic potential was investigated using an MTT assay. It was observed that genistein significantly increased BMSC cell proliferation in a time- and dose-dependent manner (P<0.01). In addition, reverse transcription-quantitative polymerase chain reaction revealed that genistein significantly inhibited the expression of runt-related transcription factor 2 (Runx2), type I collagen (Col I) and osteocalcin (OC; P<0.01). Furthermore, 20 µm genistein significantly inhibited the activity of alkaline phosphatase (ALP) and increased the activity of triglycerides (TGs) increased (P<0.01) as determined by an enzyme-linked immunosorbent assay. Finally, western blotting revealed that BMSC pretreatment with 20 µm genistein significantly increased peroxisome proliferator-activated receptor γ (PPARγ) protein expression (P<0.01). This suggests that the downregulation of PPARγ may significantly reduce the effect of genistein on cell proliferation, suppress the expression of Runx2, Col I and OC mRNA, and reduce ALP and promote TG activity in BMSCs. Thus, the results of the present study conclude that genistein induces adipogenic differentiation in human BMSCs and suppresses their osteogenic potential by upregulating the expression of PPARγ. In conclusion, genistein may be a promising candidate drug for treatment against osteogenesis.
authors.affiliation: Department of Orthopedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China; First Department of Orthopedics, The Affiliated Hospital of Beihua University, Jilin, Jilin 132001, P.R. China.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: First Department of Orthopedics, The Affiliated Hospital of Beihua University, Jilin, Jilin 132001, P.R. China.
authors.forename: Hao-Gang
authors.initials: HG
authors.lastname: Xue
authors.affiliation: Department of Orthopedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Ji-Ying
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chai
authors.affiliation: Department of Orthopedics, General Hospital of Chinese People's Liberation Army, Beijing 100853, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ni
keywords: adipogenic; bone marrow mesenchymal stem cells; genistein; osteogenic; peroxisome proliferator-activated receptor-γ