PMID- 33897442
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210428
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Microbial Metabolite Sodium Butyrate Attenuates Cartilage Degradation by 
      Restoring Impaired Autophagy and Autophagic Flux in Osteoarthritis Development.
PG  - 659597
LID - 10.3389/fphar.2021.659597 [doi]
LID - 659597
AB  - Osteoarthritis (OA) is a degenerative joint disease with multiple etiologies that 
      affects individuals worldwide. No effective interventions are currently available 
      to reverse the pathological process of OA. Sodium butyrate (NaB), a component of 
      short-chain fatty acids (SCFAs), has multiple biological activities, including 
      the attenuation of inflammation and anti-tumor activities in various diseases. 
      However, whether the protective effects of NaB in OA are associated with the 
      promotion of autophagy had not been investigated. Here, we explored the 
      chondroprotective properties of NaB in an interleukin (IL)-1beta-induced 
      inflammatory chondrocyte model and an anterior cruciate ligament transection 
      (ACLT) mouse model. Hematoxylin and eosin (HE), Safranin O, and 
      immunohistochemical staining were performed to evaluate the effects of NaB 
      treatment on articular cartilage. An optimal NaB dose for chondrocyte treatment 
      was determined via cell counting kit-8 assays. Immunofluorescence and 
      transmission electron microscopy were used to detect autophagy in chondrocytes. 
      Flow cytometry was utilized to detect reactive oxygen species (ROS), cell cycle 
      activity, and apoptosis in chondrocytes. Western blot and immunostaining were 
      performed to evaluate the protein expression levels of relevant indicators. We 
      found that the administration of NaB by oral gavage could attenuate cartilage 
      degradation. In parallel, NaB treatment could enhance the activation of 
      autophagy, increase autophagic flux, decrease extracellular matrix degradation, 
      and reduce apoptosis by restraining inflammation, ROS production, and cell cycle 
      arrest in IL-1beta-treated chondrocytes. The protective effects of NaB could be 
      partially abolished by the autophagy inhibitor 3-methyladenine (3-MA), which 
      indicated that the protective effects of NaB against OA were partially governed 
      by the enhancement of autophagy to restrain the formation of inflammatory 
      mediators and ROS and regulate cell cycle progression and apoptosis in 
      chondrocytes. In conclusion, NaB could attenuate OA progression by restoring 
      impaired autophagy and autophagic flux via the phosphoinositide 3-kinase 
      (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, both 
      in vitro and in vivo, implying that NaB could represent a novel therapeutic 
      approach for OA.
CI  - Copyright (c) 2021 Zhou, Li, Wang, Jiang, Li, Wang, Wang, Ma and Cao.
FAU - Zhou, Haikang
AU  - Zhou H
AD  - Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical 
      University, Urumqi, China.
FAU - Li, Guoqing
AU  - Li G
AD  - Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical 
      University, Urumqi, China.
FAU - Wang, Yang
AU  - Wang Y
AD  - Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical 
      University, Urumqi, China.
FAU - Jiang, Rendong
AU  - Jiang R
AD  - Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical 
      University, Urumqi, China.
FAU - Li, Yicheng
AU  - Li Y
AD  - Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical 
      University, Urumqi, China.
FAU - Wang, Huhu
AU  - Wang H
AD  - Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical 
      University, Urumqi, China.
FAU - Wang, Fei
AU  - Wang F
AD  - Xinjiang Uygur Autonomous Region Clinical Research Center for Orthopedic 
      Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 
      China.
FAU - Ma, Hairong
AU  - Ma H
AD  - Xinjiang Uygur Autonomous Region Clinical Research Center for Orthopedic 
      Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 
      China.
FAU - Cao, Li
AU  - Cao L
AD  - Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical 
      University, Urumqi, China.
LA  - eng
PT  - Journal Article
DEP - 20210409
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8062861
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - osteoarthritis
OT  - oxidative stress
OT  - sodium butyrate
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- 2021/04/27 06:00
MHDA- 2021/04/27 06:01
PMCR- 2021/04/09
CRDT- 2021/04/26 05:48
PHST- 2021/01/28 00:00 [received]
PHST- 2021/03/01 00:00 [accepted]
PHST- 2021/04/26 05:48 [entrez]
PHST- 2021/04/27 06:00 [pubmed]
PHST- 2021/04/27 06:01 [medline]
PHST- 2021/04/09 00:00 [pmc-release]
AID - 659597 [pii]
AID - 10.3389/fphar.2021.659597 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Apr 9;12:659597. doi: 10.3389/fphar.2021.659597. 
      eCollection 2021.