PMID- 33344440
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201222
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 8
DP  - 2020
TI  - Nesfatin-1 Promotes the Osteogenic Differentiation of Tendon-Derived Stem Cells 
      and the Pathogenesis of Heterotopic Ossification in Rat Tendons via the mTOR 
      Pathway.
PG  - 547342
LID - 10.3389/fcell.2020.547342 [doi]
LID - 547342
AB  - Heterotopic ossification (HO) is a pathological condition involved in 
      tendinopathy. Adipokines are known to play a key role in HO of tendinopathy. 
      Nesfatin-1, an 82-amino acid adipokine is closely reportedly associated with 
      diabetes mellitus (DM), which, in turn, is closely related to tendinopathy. In 
      the present study, we aimed to investigate the effects of nesfatin-1 on the 
      osteogenic differentiation of tendon-derived stem cells (TDSCs) and the 
      pathogenesis of tendinopathy in rats. In vitro, TDSCs were incubated in 
      osteogenic induction medium for 14 days with different nesfatin-1 concentration. 
      In vivo, Sprague Dawley rats underwent Achilles tenotomy to evaluate the effect 
      of nesfatin-1 on tendinopathy. Our results showed that the expression of 
      nesfatin-1 expression in tendinopathy patients was significantly higher than that 
      in healthy subjects. Nesfatin-1 affected the cytoskeleton and reduced the 
      migration ability of TDSCs in vitro. Furthermore, nesfatin-1 inhibited the 
      expression of Scx, Mkx, and Tnmd and promoted the expression of osteogenic genes, 
      such as COL1a1, ALP, and RUNX2; these results suggested that nesfatin-1 inhibits 
      cell migration, adversely impacts tendon phenotype, promotes osteogenic 
      differentiation of TDSCs and the pathogenesis of HO in rat tendons. Moreover, we 
      observed that nesfatin-1 suppressed autophagy and activated the mammalian target 
      of rapamycin (mTOR) pathway both in vitro and in vivo. The suppression of the 
      mTOR pathway alleviated nesfatin-1-induced HO development in rat tendons. Thus, 
      nesfatin-1 promotes the osteogenic differentiation of TDSC and the pathogenesis 
      of HO in rat tendons via the mTOR pathway; these findings highlight a new 
      potential therapeutic target for tendinopathy.
CI  - Copyright (c) 2020 Xu, Zhang, Chen, Moqbel, He, Ma, Jiang, Xiong and Wu.
FAU - Xu, Kai
AU  - Xu K
AD  - Department of Orthopedic Surgery, The Second Affiliated Hospital, School of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Zhang, Zhanfeng
AU  - Zhang Z
AD  - Department of Orthopedic Surgery, The Second Affiliated Hospital, School of 
      Medicine, Zhejiang University, Hangzhou, China.
AD  - Department of Orthopedic Surgery, The First People's Hospital of Huzhou, Huzhou, 
      China.
FAU - Chen, Mengyao
AU  - Chen M
AD  - Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, China.
FAU - Moqbel, Safwat Adel Abdo
AU  - Moqbel SAA
AD  - Department of Orthopedic Surgery, The Second Affiliated Hospital, School of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - He, Yuzhe
AU  - He Y
AD  - Department of Orthopedic Surgery, The Second Affiliated Hospital, School of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Ma, Chiyuan
AU  - Ma C
AD  - Department of Orthopedic Surgery, The Second Affiliated Hospital, School of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Jiang, Lifeng
AU  - Jiang L
AD  - Department of Orthopedic Surgery, The Second Affiliated Hospital, School of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Xiong, Yan
AU  - Xiong Y
AD  - Department of Orthopedic Surgery, The Second Affiliated Hospital, School of 
      Medicine, Zhejiang University, Hangzhou, China.
FAU - Wu, Lidong
AU  - Wu L
AD  - Department of Orthopedic Surgery, The Second Affiliated Hospital, School of 
      Medicine, Zhejiang University, Hangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20201203
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC7744791
OTO - NOTNLM
OT  - mTOR pathway
OT  - nesfatin-1
OT  - osteogenic tendon differentiation
OT  - tendinopathy
OT  - tendon-derived stem cells
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2020/12/22 06:00
MHDA- 2020/12/22 06:01
PMCR- 2020/01/01
CRDT- 2020/12/21 06:08
PHST- 2020/03/31 00:00 [received]
PHST- 2020/11/13 00:00 [accepted]
PHST- 2020/12/21 06:08 [entrez]
PHST- 2020/12/22 06:00 [pubmed]
PHST- 2020/12/22 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2020.547342 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2020 Dec 3;8:547342. doi: 10.3389/fcell.2020.547342. 
      eCollection 2020.