PMID- 27706709
OWN - NLM
STAT- MEDLINE
DCOM- 20170208
LR  - 20201209
IS  - 1676-5680 (Electronic)
IS  - 1676-5680 (Linking)
VI  - 15
IP  - 3
DP  - 2016 Sep 9
TI  - Growth factor progranulin blocks tumor necrosis factor-alpha-mediated inhibition of 
      osteoblast differentiation.
LID - 10.4238/gmr.15038126 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) stimulates osteoclast differentiation and 
      suppresses osteoblast differentiation, leading to bone loss and decreased bone 
      mass in local inflammation areas in patients with rheumatoid arthritis. The 
      growth factor progranulin (PGRN) is expressed in various types of cells and play 
      crucial roles in the pathogenesis of atherosclerosis and arthritis by blocking 
      TNF-alpha. Here, we investigated the role of PGRN in blocking TNF-alpha-mediated 
      inhibition of osteoblast differentiation and the regulatory mechanism. C2C12 stem 
      cell was induced by bone morphogenetic protein-2 (BMP-2) for osteoblast 
      differentiation. A significant increase in ALP activity (P < 0.001), as well as 
      the expression of ColI, Ocn, and Bsp in the induced cells (P < 0.01 and P < 
      0.001) were observed; the marker gene expression and ALP activity were inhibited 
      by TNF-alpha (P < 0.01 and P < 0.001). PGRN significantly blocks the TNF-alpha-mediated 
      inhibition of osteoblast differentiation, evidenced by the ALP activity (P < 0.05 
      and P < 0.01), Alizarin red staining, the expression of ColI, Ocn, and Bsp (P < 
      0.05 and P < 0.01) and the osteoblast key transcription factor gene Runx2 (P < 
      0.01), Osx (P < 0.05), and ATF4 (P < 0.05). Mechanical study indicated that PGRN 
      significantly blocks the TNF-alpha-mediated stimulation of NF-kB signaling (P < 0.01 
      and P < 0.001). PGRN exerts a protective effect on osteoblast differentiation in 
      an inflammatory environment. Thus, we concluded that the treatment of osteoblasts 
      with PGRN could be used in the future to prevent or treat rheumatoid 
      arthritis-associated bone loss.
FAU - Wang, N
AU  - Wang N
AD  - Department of Rehabilitation, Linyi People's Hospital, Linyi, China.
FAU - Zhang, J
AU  - Zhang J
AD  - Department of Rehabilitation, Linyi People's Hospital, Linyi, China.
FAU - Yang, J X
AU  - Yang JX
AD  - Department of Orthopedics, Linyi People's Hospital, Linyi, China 
      yangjianxun10281@163.com.
LA  - eng
PT  - Journal Article
DEP - 20160909
PL  - Brazil
TA  - Genet Mol Res
JT  - Genetics and molecular research : GMR
JID - 101169387
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Atrnl1 protein, mouse)
RN  - 0 (Collagen Type I)
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (Granulins)
RN  - 0 (Grn protein, mouse)
RN  - 0 (Ibsp protein, mouse)
RN  - 0 (Integrin-Binding Sialoprotein)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Progranulins)
RN  - 0 (Runx2 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/metabolism
MH  - Animals
MH  - *Cell Differentiation
MH  - Cell Line
MH  - Collagen Type I/genetics/metabolism
MH  - Core Binding Factor Alpha 1 Subunit/genetics/metabolism
MH  - Granulins
MH  - Integrin-Binding Sialoprotein/genetics/metabolism
MH  - Intercellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Membrane Proteins/genetics/metabolism
MH  - Mice
MH  - Osteoblasts/cytology/drug effects/*metabolism
MH  - Progranulins
MH  - Tumor Necrosis Factor-alpha/pharmacology
COIS- The authors declare no conflict of interest.
EDAT- 2016/10/06 06:00
MHDA- 2017/02/09 06:00
CRDT- 2016/10/06 06:00
PHST- 2016/10/06 06:00 [entrez]
PHST- 2016/10/06 06:00 [pubmed]
PHST- 2017/02/09 06:00 [medline]
AID - gmr8126 [pii]
AID - 10.4238/gmr.15038126 [doi]
PST - epublish
SO  - Genet Mol Res. 2016 Sep 9;15(3). doi: 10.4238/gmr.15038126.