PMID- 27917698
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20211204
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Linking)
VI  - 26
IP  - 6
DP  - 2017 Mar 15
TI  - Tetramethylpyrazine Protects Against Glucocorticoid-Induced Apoptosis by 
      Promoting Autophagy in Mesenchymal Stem Cells and Improves Bone Mass in 
      Glucocorticoid-Induced Osteoporosis Rats.
PG  - 419-430
LID - 10.1089/scd.2016.0233 [doi]
AB  - Glucocorticoid-induced osteoporosis (GIOP) is a widespread clinical complication 
      due to the common use of glucocorticoids. Excess glucocorticoids induce apoptosis 
      of bone marrow-derived mesenchymal stem cells (BMSCs), which have been shown to 
      play an increasingly important role in the pathogenesis and therapy of 
      osteoporosis. Tetramethylpyrazine (TMP), an extract from one of the most 
      recognized herbs in traditional Chinese medicine (Chuanxiong), has been reported 
      to have antiapoptotic properties. In this study, we tested whether TMP protects 
      rat BMSCs following exposure to glucocorticoids in vitro and in vivo. We treated 
      BMSCs with different concentrations of TMP (50, 100, or 200 muM) and exposed them 
      to 10(-6) M dexamethasone (Dex) for 48 h in vitro. Our data showed that TMP 
      inhibited Dex-induced cytotoxicity and protected BMSCs from apoptosis. 
      Interestingly, further results demonstrated that TMP prevented apoptosis in BMSCs 
      by promoting autophagy in an AMP-activated protein kinase (AMPK) and mammalian 
      target of rapamycin (mTOR) pathway-dependent manner. In addition, calcein 
      fluorescence double labeling and microcomputed tomography scanning indicated that 
      12 weeks of TMP administration augmented bone formation and protected trabecular 
      bone mass in GIOP rats. We also discovered that first-passage BMSCs isolated from 
      the TMP treatment group had a lower rate of apoptosis and a higher light chain 3 
      (LC3)-II/LC3-I ratio than the GIOP group. Our findings demonstrate for the first 
      time that TMP can protect BMSCs from exposure to excess glucocorticoids by 
      promoting autophagy through AMPK/mTOR pathway and might be an effective agent for 
      the prevention and treatment of GIOP.
FAU - Wang, Long
AU  - Wang L
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
FAU - Zhang, Hong-Yang
AU  - Zhang HY
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
FAU - Gao, Bo
AU  - Gao B
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
FAU - Shi, Jun
AU  - Shi J
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
FAU - Huang, Qiang
AU  - Huang Q
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
FAU - Han, Yue-Hu
AU  - Han YH
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
FAU - Hu, Ya-Qian
AU  - Hu YQ
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
FAU - Lu, Wei-Guang
AU  - Lu WG
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
FAU - Zhao, Zhuo-Jie
AU  - Zhao ZJ
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
FAU - Liu, Bao-Hua
AU  - Liu BH
AD  - 2 Health Science Center, Shenzhen University , Shenzhen, People's Republic of 
      China .
FAU - Jie, Qiang
AU  - Jie Q
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
FAU - Yang, Liu
AU  - Yang L
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
FAU - Luo, Zhuo-Jing
AU  - Luo ZJ
AD  - 1 Institute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical 
      University , Xi'an, People's Republic of China .
LA  - eng
PT  - Journal Article
DEP - 20170104
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (Glucocorticoids)
RN  - 0 (Protective Agents)
RN  - 0 (Pyrazines)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - V80F4IA5XG (tetramethylpyrazine)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Bone and Bones/drug effects/*pathology
MH  - Dexamethasone
MH  - Glucocorticoids/*adverse effects
MH  - Mesenchymal Stem Cells/*cytology/drug effects/metabolism
MH  - Organ Size/drug effects
MH  - Osteogenesis/drug effects
MH  - Osteoporosis/*chemically induced/*drug therapy/pathology
MH  - Protective Agents/pharmacology/therapeutic use
MH  - Pyrazines/pharmacology/*therapeutic use
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - autophagy
OT  - bone marrow-derived mesenchymal stem cells
OT  - glucocorticoids
OT  - osteoporosis
OT  - tetramethylpyrazine
EDAT- 2016/12/06 06:00
MHDA- 2017/09/19 06:00
CRDT- 2016/12/06 06:00
PHST- 2016/12/06 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
PHST- 2016/12/06 06:00 [entrez]
AID - 10.1089/scd.2016.0233 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2017 Mar 15;26(6):419-430. doi: 10.1089/scd.2016.0233. Epub 2017 
      Jan 4.