PMID- 31173178
OWN - NLM
STAT- MEDLINE
DCOM- 20191223
LR  - 20211204
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 44
IP  - 2
DP  - 2019 Aug
TI  - Strontium promotes osteogenic differentiation by activating autophagy via the the 
      AMPK/mTOR signaling pathway in MC3T3‑E1 cells.
PG  - 652-660
LID - 10.3892/ijmm.2019.4216 [doi]
AB  - Strontium (Sr) is an alkaline earth metal that exerts the dual effect of 
      improving bone formation and suppressing bone resorption, resulting in increased 
      bone apposition rates and bone mineral density. However, the mechanisms through 
      which Sr exerts these beneficial effects on bone have yet to be fully elucidated. 
      The present study aimed to reveal the underlying molecular mechanisms associated 
      with Sr‑induced osteogenic differentiation. The effects of Sr on cell 
      proliferation and osteogenic differentiation were analyzed by MTT assay, RT‑qPCR, 
      western blot analysis, alkaline phosphatase (ALP) and Alizarin red staining 
      assays. The extent of autophagy was determined by monodansylcadaverine (MDC) 
      staining and western blot analysis of two markers of cellular autophagic 
      activity, the steatosis‑associated protein, sequestosome‑1 (SQSTM1/p62), and the 
      two isoforms of microtubule‑associated protein 1 light chain 3 (LC3), LC‑3‑I/II. 
      The expression levels of AMP‑activated protein kinase (AMPK) and mammalian target 
      of rapamycin (mTOR) were also detected by western blot analysis. Sr at a 
      concentration of 3 mM exerted the most pronounced effect on osteogenic 
      differentiation, without any apparent cell toxicity. At the same time, cellular 
      autophagy was active during this process. Subsequently, autophagy was blocked by 
      3‑methyladenine, and the enhancement of osteogenic differentiation in response to 
      Sr was abrogated. Additionally, the phosphorylation level of AMPK was 
      significantly increased, whereas that of mTOR was significantly decreased, in the 
      Sr‑treated group. Taken together, the findings of the present study demonstrate 
      that Sr stimulates AMPK‑activated autophagy to induce the osteogenic 
      differentiation of MC3T3‑E1 cells.
FAU - Cheng, You
AU  - Cheng Y
AD  - School of Medical Laboratory, Tianjin Medical University, Tianjin 300070, P.R. 
      China.
FAU - Huang, Lunhui
AU  - Huang L
AD  - School of Medical Laboratory, Tianjin Medical University, Tianjin 300070, P.R. 
      China.
FAU - Wang, Yichao
AU  - Wang Y
AD  - Department of Clinical Laboratory Medicine, Taizhou University Hospital, Taizhou, 
      Zhejiang 318000, P.R. China.
FAU - Huo, Qianyu
AU  - Huo Q
AD  - School of Medical Laboratory, Tianjin Medical University, Tianjin 300070, P.R. 
      China.
FAU - Shao, Yanhong
AU  - Shao Y
AD  - School of Medical Laboratory, Tianjin Medical University, Tianjin 300070, P.R. 
      China.
FAU - Bao, Huijing
AU  - Bao H
AD  - School of Medical Laboratory, Tianjin Medical University, Tianjin 300070, P.R. 
      China.
FAU - Li, Zhaoyang
AU  - Li Z
AD  - School of Materials Science and Engineering, Tianjin University, Tianjin 300350, 
      P.R. China.
FAU - Liu, Yunde
AU  - Liu Y
AD  - School of Medical Laboratory, Tianjin Medical University, Tianjin 300070, P.R. 
      China.
FAU - Li, Xue
AU  - Li X
AD  - School of Medical Laboratory, Tianjin Medical University, Tianjin 300070, P.R. 
      China.
LA  - eng
PT  - Journal Article
DEP - 20190530
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - YZS2RPE8LE (Strontium)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Mice
MH  - Osteogenesis/*drug effects
MH  - Signal Transduction/drug effects
MH  - Strontium/*pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC6605659
EDAT- 2019/06/08 06:00
MHDA- 2019/12/24 06:00
PMCR- 2019/05/30
CRDT- 2019/06/08 06:00
PHST- 2019/01/09 00:00 [received]
PHST- 2019/05/24 00:00 [accepted]
PHST- 2019/06/08 06:00 [pubmed]
PHST- 2019/12/24 06:00 [medline]
PHST- 2019/06/08 06:00 [entrez]
PHST- 2019/05/30 00:00 [pmc-release]
AID - ijmm-44-02-0652 [pii]
AID - 10.3892/ijmm.2019.4216 [doi]
PST - ppublish
SO  - Int J Mol Med. 2019 Aug;44(2):652-660. doi: 10.3892/ijmm.2019.4216. Epub 2019 May 
      30.