PMID- 38342566
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240216
IS  - 1875-5364 (Electronic)
IS  - 1875-5364 (Linking)
VI  - 22
IP  - 2
DP  - 2024 Feb
TI  - Activation of NRF2 by celastrol increases antioxidant functions and prevents the 
      progression of osteoarthritis in mice.
PG  - 137-145
LID - S1875-5364(24)60586-8 [pii]
LID - 10.1016/S1875-5364(24)60586-8 [doi]
AB  - Excessive oxidative stress impairs cartilage matrix metabolism balance, 
      significantly contributing to osteoarthritis (OA) development. Celastrol (CSL), a 
      drug derived from Tripterygium wilfordii, has recognized applications in the 
      treatment of cancer and immune system disorders, yet its antioxidative stress 
      mechanisms in OA remain underexplored. This study aimed to substantiate CSL's 
      chondroprotective effects and unravel its underlying mechanisms. We investigated 
      CSL's impact on chondrocytes under both normal and inflammatory conditions. In 
      vitro, CSL mitigated interleukin (IL)-1beta-induced activation of proteinases and 
      promoted cartilage extracellular matrix (ECM) synthesis. In vivo, intra-articular 
      injection of CSL ameliorated cartilage degeneration and mitigated subchondral 
      bone lesions in OA mice. Mechanistically, it was found that inhibiting nuclear 
      factor erythroid 2-related factor 2 (NRF2) abrogated CSL-mediated antioxidative 
      functions and exacerbated the progression of OA. This study is the first to 
      elucidate the role of CSL in the treatment of OA through the activation of NRF2, 
      offering a novel therapeutic avenue for arthritis therapy.
CI  - Copyright (c) 2024 China Pharmaceutical University. Published by Elsevier B.V. All 
      rights reserved.
FAU - Liu, Mingming
AU  - Liu M
AD  - Department of Orthopedic Surgery, The Affiliated Lianyungang Clinical College of 
      Xuzhou Medical University (The Second People's Hospital of Lianyungang), 
      Lianyungang 222003, China.
FAU - Guo, Jiatian
AU  - Guo J
AD  - Department of Orthopedic Surgery, The Affiliated Lianyungang Clinical College of 
      Xuzhou Medical University (The Second People's Hospital of Lianyungang), 
      Lianyungang 222003, China.
FAU - Zhao, Jing
AU  - Zhao J
AD  - Department of Orthopedic Surgery, The Affiliated Lianyungang Clinical College of 
      Xuzhou Medical University (The Second People's Hospital of Lianyungang), 
      Lianyungang 222003, China.
FAU - Li, Hongye
AU  - Li H
AD  - Department of Orthopedic Surgery, The Affiliated Lianyungang Clinical College of 
      Xuzhou Medical University (The Second People's Hospital of Lianyungang), 
      Lianyungang 222003, China.
FAU - Feng, Xiaoxiao
AU  - Feng X
AD  - Department of Orthopedic Surgery, The Affiliated Lianyungang Clinical College of 
      Xuzhou Medical University (The Second People's Hospital of Lianyungang), 
      Lianyungang 222003, China.
FAU - Liu, Haojun
AU  - Liu H
AD  - Department of Orthopedic Surgery, The Affiliated Lianyungang Clinical College of 
      Xuzhou Medical University (The Second People's Hospital of Lianyungang), 
      Lianyungang 222003, China.
FAU - Zhang, Hao
AU  - Zhang H
AD  - Department of Orthopedic Surgery, The Affiliated Lianyungang Clinical College of 
      Xuzhou Medical University (The Second People's Hospital of Lianyungang), 
      Lianyungang 222003, China.
FAU - Jia, Xuejun
AU  - Jia X
AD  - Department of Orthopedic Surgery, The Affiliated Lianyungang Clinical College of 
      Xuzhou Medical University (The Second People's Hospital of Lianyungang), 
      Lianyungang 222003, China.
FAU - Wei, Rushuai
AU  - Wei R
AD  - Department of Orthopedic Surgery, The Affiliated Lianyungang Clinical College of 
      Xuzhou Medical University (The Second People's Hospital of Lianyungang), 
      Lianyungang 222003, China.
FAU - Li, Fang
AU  - Li F
AD  - Department of Orthopedic Surgery, The Affiliated Lianyungang Clinical College of 
      Xuzhou Medical University (The Second People's Hospital of Lianyungang), 
      Lianyungang 222003, China.
FAU - Chen, Chong
AU  - Chen C
AD  - Institute of Hematology, Xuzhou Medical University, Xuzhou 221004, China.
FAU - Hou, Mingzhuang
AU  - Hou M
AD  - Department of Orthopaedics, The First Afliated Hospital of Soochow University, 
      Soochow University, Suzhou 215006, China. Electronic address: xhy_8@163.com.
FAU - Lv, Nanning
AU  - Lv N
AD  - Department of Orthopedic Surgery, The Affiliated Lianyungang Clinical College of 
      Xuzhou Medical University (The Second People's Hospital of Lianyungang), 
      Lianyungang 222003, China. Electronic address: lvnanning123@163.com.
FAU - Xu, Haiyan
AU  - Xu H
AD  - Department of human anatomy, Xuzhou Medical University, Xuzhou 221004, China. 
      Electronic address: houmingzhuangyll@163.com.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Chin J Nat Med
JT  - Chinese journal of natural medicines
JID - 101504416
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Antioxidants)
RN  - L8GG98663L (celastrol)
RN  - 0 (Pentacyclic Triterpenes)
RN  - 0 (Interleukin-1beta)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *NF-E2-Related Factor 2/genetics/metabolism
MH  - Antioxidants/pharmacology/metabolism
MH  - *Osteoarthritis/drug therapy/metabolism/pathology
MH  - Pentacyclic Triterpenes/pharmacology/metabolism
MH  - Chondrocytes
MH  - Interleukin-1beta
OTO - NOTNLM
OT  - Articular cartilage
OT  - Celastrol
OT  - Extracellular matrix
OT  - NRF2
OT  - Osteoarthritis
EDAT- 2024/02/12 05:43
MHDA- 2024/02/12 05:44
CRDT- 2024/02/11 20:59
PHST- 2023/08/26 00:00 [received]
PHST- 2024/02/12 05:44 [medline]
PHST- 2024/02/12 05:43 [pubmed]
PHST- 2024/02/11 20:59 [entrez]
AID - S1875-5364(24)60586-8 [pii]
AID - 10.1016/S1875-5364(24)60586-8 [doi]
PST - ppublish
SO  - Chin J Nat Med. 2024 Feb;22(2):137-145. doi: 10.1016/S1875-5364(24)60586-8.