GPR120: A bi-potential mediator to modulate the osteogenic and adipogenic differentiation of BMMSCs
Authors: Bo Gao
Li Chen
Jian Liu
Xiao-Jie Li
Qiang Jie
Long Wang
Qiang Huang
Bao-Hua Liu
Ya-Qian Hu
Liu Yang
Zhen Sun
Zhuo-Jing Luo
Wei-Guang Lu
Journal: Scientific Reports (2015)
Discipline: Multidisciplinary
Keywords: Free fatty acids; GPCRs; GPR120; adipogenesis; osteogenesis
Affiliations: Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, People's Republic of China., Lanzhou General Hospital of Lanzhou Military Command, Lanzhou Gansu, 730050, People's Republic of China., KMEB, Molecular Endocrinology, Campusvej 55, DK-5230 Odense M, Denmark., Health Science Center, Shenzhen University, 3688 Nanhai Ave, Shenzhen 518060, People's Republic of China.

Abstract:  Free fatty acids display diverse effects as signalling molecules through GPCRs in addition to their involvement in cellular metabolism. GPR120, a G protein-coupled receptor for long-chain unsaturated fatty acids, has been reported to mediate adipogenesis in lipid metabolism. However, whether GPR120 also mediates osteogenesis and regulates BMMSCs remain unclear. In this study, we showed that GPR120 targeted the bi-potential differentiation of BMMSCs in a ligand dose-dependent manner. High concentrations of TUG-891 (a highly selective agonist of GPR120) promoted osteogenesis via the Ras-ERK1/2 cascade, while low concentrations elevated P38 and increased adipogenesis. The fine molecular regulation of GPR120 was implemented by up-regulating different integrin subunits (Œ±1, Œ±2 and Œ≤1; Œ±5 and Œ≤3). The administration of high doses of TUG-891 rescued oestrogen-deficient bone loss in vivo, further supporting an essential role of GPR120 in bone metabolism. Our findings, for the first time, showed that GPR120-mediated cellular signalling determines the bi-potential differentiation of BMMSCs in a dose-dependent manner. Additionally, the induction of different integrin subunits was involved in the cytoplasmic regulation of a seesaw-like balance between ERK and p38 phosphorylation. These findings provide new hope for developing novel remedies to treat osteoporosis by adjusting the GPR120-mediated differentiation balance of BMMSCs. 

Retracted: No

PubPeer comments:
 Similar images in 2 different treatment regimes  , 
 Thanks for pointing out the mistake. In given figure 2 (a) the image of hypothalamus 6u00b5g u2013 R (after 4 h of rotenone (R) injection) is wrongly pasted. This happened during processing and compilation of all 36 mages in one figure. However, both the images of frontal cortex and hypothalamus did not have any signal of GFAP immunoreactivity and did not affect the conclusion of study. Please find the amended image of the same in attachment.  , 
 There are a few more areas of overlaps in three of the figures: Fig3a:  Fig 5:  Fig7a:  , 
 Fig 4a may benefit from a correction too.  , 
 #3 Please find the replaced images however, I would like to bring your kind attention that the images are from rat brain sections and neuronal cells after treatment as given in article. Please find the uploaded images. In total there were 72 images in panel and you may have a look. The conclusion of study absolutely remain same with these changes.  , 
 #4 The images are corrected however, I would like to bring your kind attention that the inadvertent error happened in control and vehicle only and this does not affect the conclusion of study.  ,