PMID- 26622487
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220310
IS  - 1792-0981 (Print)
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Linking)
VI  - 10
IP  - 4
DP  - 2015 Oct
TI  - Rapamycin-induced autophagy activity promotes bone fracture healing in rats.
PG  - 1327-1333
AB  - Autophagy is a crucial mediating process for normal bone cell function and 
      metabolism in physiology or pathology. Rapamycin has been demonstrated to induce 
      the autophagy pathway by inhibiting the mammalian target of rapamycin (mTOR) 
      pathway. However, the contribution of autophagy in orthopedic diseases is rarely 
      reported. The aim of the present study was to evaluate the capacity of 
      pharmacologically induced autophagy to modify disease function in a rat model of 
      bone fracture. A femur fracture model was established via surgery in adult male 
      Sprague-Dawley rats. Rapamycin (n=63 rats) or dimethyl sulfoxide (DMSO) vehicle 
      control (n=63 rats) was administered intraperitoneally for 2, 4 and 6 weeks, and 
      21 randomly selected rats were sacrificed in each group at each time point. X-ray 
      micro-computed tomography and hematoxylin and eosin staining were used to 
      evaluate the extent of fracture healing in each group. The effects of rapamycin 
      on autophagy, mTOR signaling and the expression levels of vascular endothelial 
      growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) were analyzed 
      using immunohistochemistry, immunofluorescence staining and western blot 
      analysis. Rapamycin affected the mTOR signaling pathway in rats following 
      fracture, as indicated by the inhibition of the phosphorylation of ribosomal 
      protein S6, a target of mTOR, and activation of microtubule-associated protein 2 
      light chain 3, a key marker of autophagy. Histomorphometry and image examination 
      indicated that the number of osteoblasts in each section was significantly 
      (P<0.01) increased in the rapamycin group compared with the control group, and 
      this was associated with a significant (P<0.05) increase in mineralized callus 
      fraction. Furthermore, rapamycin treatment increased the expression levels of 
      VEGF and PCNA in the rat callus tissue. These results suggest that rapamycin may 
      serve a beneficial function in fracture healing, and that the underlying 
      mechanism may involve the activation of autophagy.
FAU - Yang, G E
AU  - Yang GE
AD  - Department of Orthopedic Surgery, The Affiliated Southeast Hospital of Xiamen 
      University, Orthopedic Center of People's Liberation Army, Zhangzhou, Fujian 
      363000, P.R. China.
FAU - Duan, Xunhong
AU  - Duan X
AD  - Department of Orthopedic Surgery, The Affiliated Southeast Hospital of Xiamen 
      University, Orthopedic Center of People's Liberation Army, Zhangzhou, Fujian 
      363000, P.R. China.
FAU - Lin, Dasheng
AU  - Lin D
AD  - Department of Orthopedic Surgery, The Affiliated Southeast Hospital of Xiamen 
      University, Orthopedic Center of People's Liberation Army, Zhangzhou, Fujian 
      363000, P.R. China.
FAU - Li, Ten
AU  - Li T
AD  - Department of Orthopedic Surgery, The Affiliated Southeast Hospital of Xiamen 
      University, Orthopedic Center of People's Liberation Army, Zhangzhou, Fujian 
      363000, P.R. China.
FAU - Luo, Deqing
AU  - Luo D
AD  - Department of Orthopedic Surgery, The Affiliated Southeast Hospital of Xiamen 
      University, Orthopedic Center of People's Liberation Army, Zhangzhou, Fujian 
      363000, P.R. China.
FAU - Wang, Lei
AU  - Wang L
AD  - Department of Orthopedic Surgery, The Affiliated Southeast Hospital of Xiamen 
      University, Orthopedic Center of People's Liberation Army, Zhangzhou, Fujian 
      363000, P.R. China.
FAU - Lian, Kejian
AU  - Lian K
AD  - Department of Orthopedic Surgery, The Affiliated Southeast Hospital of Xiamen 
      University, Orthopedic Center of People's Liberation Army, Zhangzhou, Fujian 
      363000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20150727
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
EIN - Exp Ther Med. 2021 Apr;21(4):318. PMID: 33868465
PMC - PMC4577952
OTO - NOTNLM
OT  - autophagy
OT  - bone fracture healing
OT  - rapamycin
EDAT- 2015/12/02 06:00
MHDA- 2015/12/02 06:01
PMCR- 2015/07/27
CRDT- 2015/12/02 06:00
PHST- 2014/08/23 00:00 [received]
PHST- 2015/06/01 00:00 [accepted]
PHST- 2015/12/02 06:00 [entrez]
PHST- 2015/12/02 06:00 [pubmed]
PHST- 2015/12/02 06:01 [medline]
PHST- 2015/07/27 00:00 [pmc-release]
AID - ETM-0-0-2660 [pii]
AID - 10.3892/etm.2015.2660 [doi]
PST - ppublish
SO  - Exp Ther Med. 2015 Oct;10(4):1327-1333. doi: 10.3892/etm.2015.2660. Epub 2015 Jul 
      27.