PMID- 37789884
OWN - NLM
STAT- MEDLINE
DCOM- 20231102
LR  - 20231102
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2023
DP  - 2023
TI  - Betulinic Acid Attenuates Osteoarthritis via Limiting NLRP3 Inflammasome 
      Activation to Decrease Interleukin-1beta Maturation and Secretion.
PG  - 3706421
LID - 10.1155/2023/3706421 [doi]
LID - 3706421
AB  - INTRODUCTION: Osteoarthritis (OA) is the most common degenerative joint disorder. 
      Prior studies revealed that activation of NLRP3 inflammasome could promote the 
      activation and secretion of interleukin-1beta (IL-1beta), which has an adverse effect 
      on the progression of OA. Betulinic acid (BA) is a compound extract of birch, 
      whether it can protect against OA and the mechanisms involved are still unknown. 
      MATERIALS AND METHODS: In vivo experiments, using gait analysis, ELISA, micro-CT, 
      and scanning electron microscopy (SEM), histological staining, immunohistological 
      (IHC) and immunofluorescence (IF) staining, and atomic force microscopy (AFM) to 
      assess OA progression after intraperitoneal injection of 5 and 15 mg/kg BA in an 
      OA mouse model. In vitro experiments, caspase-1, IL-1beta, and the N-terminal 
      fragment of gasdermin D (GSDMD-NT) were measured in bone marrow-derived 
      macrophages (BMDMs) by using ELISA, western blot, and immunofluorescence 
      staining. RESULTS: We demonstrated that OA progression can be postponed with 
      intraperitoneal injection of 5 and 15 mg/kg BA in an OA mouse model. 
      Specifically, BA postponed DMM-induced cartilage deterioration, alleviated 
      subchondral bone sclerosis, and relieved synovial inflammation. In vitro studies, 
      the activated NLRP3 inflammasome produces mature IL-1beta by facilitating the 
      cleavage of pro-IL-1beta, and BA could inhibit the activation of NLRP3 inflammasome 
      in BMDMs. CONCLUSIONS: Taken together, our analyses revealed that BA attenuates 
      OA via limiting NLRP3 inflammasome activation to decrease the IL-1beta maturation 
      and secretion.
CI  - Copyright (c) 2023 Bo Liu et al.
FAU - Liu, Bo
AU  - Liu B
AD  - Department of Orthopaedics, People's Hospital of Leshan, 238 Baita Road, Leshan 
      614000, Sichuan, China.
AD  - Department of Orthopaedics, First Affiliated Hospital of Soochow University, 899 
      Pinghai Road, Suzhou 215006, Jiangsu, China.
AD  - Orthopaedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, 
      Jiangsu, China.
FAU - Wu, Yanglin
AU  - Wu Y
AD  - Department of Orthopaedics, First Affiliated Hospital of Soochow University, 899 
      Pinghai Road, Suzhou 215006, Jiangsu, China.
AD  - Orthopaedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, 
      Jiangsu, China.
AD  - Department of Orthopaedics, Tenth People's Hospital of Tongji University, 301 
      Middle Yanchang Road, Shanghai 200072, Shanghai, China.
FAU - Liang, Ting
AU  - Liang T
AD  - Orthopaedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, 
      Jiangsu, China.
FAU - Zhou, Yunlong
AU  - Zhou Y
AD  - Department of Orthopaedics, People's Hospital of Leshan, 238 Baita Road, Leshan 
      614000, Sichuan, China.
FAU - Chen, Guangdong
AU  - Chen G
AD  - Department of Orthopaedics, First Affiliated Hospital of Soochow University, 899 
      Pinghai Road, Suzhou 215006, Jiangsu, China.
FAU - He, Jiaheng
AU  - He J
AD  - Department of Orthopaedics, First Affiliated Hospital of Soochow University, 899 
      Pinghai Road, Suzhou 215006, Jiangsu, China.
AD  - Orthopaedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, 
      Jiangsu, China.
AD  - Department of Orthopaedics, Jiangsu Shengze Hospital, No. 1399, Market West Road, 
      Shengze 215000, Jiangsu, China.
FAU - Ji, Chenchen
AU  - Ji C
AD  - Department of Orthopaedics, First Affiliated Hospital of Soochow University, 899 
      Pinghai Road, Suzhou 215006, Jiangsu, China.
AD  - Orthopaedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, 
      Jiangsu, China.
AD  - Stroke Intensive Care Unit, Children's Hospital of Soochow University, 92 
      Zhongnan Road, Suzhou 215006, Jiangsu, China.
FAU - Liu, Peixin
AU  - Liu P
AD  - Department of Orthopaedics, First Affiliated Hospital of Soochow University, 899 
      Pinghai Road, Suzhou 215006, Jiangsu, China.
AD  - Orthopaedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, 
      Jiangsu, China.
AD  - Department of Orthopedics, Suzhou Xiangcheng People's Hospital, 1060 Huayuan 
      Road, Suzhou 215131, Jiangsu, China.
FAU - Zhang, Chenhui
AU  - Zhang C
AD  - Department of Orthopaedics, First Affiliated Hospital of Soochow University, 899 
      Pinghai Road, Suzhou 215006, Jiangsu, China.
AD  - Orthopaedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, 
      Jiangsu, China.
FAU - Lin, Jun
AU  - Lin J
AD  - Department of Orthopaedics, First Affiliated Hospital of Soochow University, 899 
      Pinghai Road, Suzhou 215006, Jiangsu, China.
AD  - Department of Orthopaedics, Suzhou Dushu Lake Hospital, Dushu Lake Hospital 
      Affiliated to Soochow University, Medical Center of Soochow University, Suzhou 
      215001, Jiangsu, China.
FAU - Shi, Kece
AU  - Shi K
AUID- ORCID: 0009-0004-5724-7829
AD  - Department of Orthopaedics, People's Hospital of Leshan, 238 Baita Road, Leshan 
      614000, Sichuan, China.
FAU - Luo, Zongping
AU  - Luo Z
AUID- ORCID: 0000-0002-0617-2597
AD  - Department of Orthopaedics, First Affiliated Hospital of Soochow University, 899 
      Pinghai Road, Suzhou 215006, Jiangsu, China.
AD  - Orthopaedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, 
      Jiangsu, China.
FAU - Liu, Naicheng
AU  - Liu N
AUID- ORCID: 0000-0002-5218-8581
AD  - Department of Orthopaedics, First Affiliated Hospital of Soochow University, 899 
      Pinghai Road, Suzhou 215006, Jiangsu, China.
FAU - Su, Xinlin
AU  - Su X
AUID- ORCID: 0000-0003-0351-5205
AD  - Department of Orthopaedics, First Affiliated Hospital of Soochow University, 899 
      Pinghai Road, Suzhou 215006, Jiangsu, China.
LA  - eng
PT  - Journal Article
DEP - 20230925
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 4G6A18707N (Betulinic Acid)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (IL1B protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Betulinic Acid
MH  - Disease Models, Animal
MH  - *Inflammasomes
MH  - Interleukin-1beta
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - *Osteoarthritis/drug therapy/pathology
PMC - PMC10545461
COIS- The authors declare that they have no competing interests.
EDAT- 2023/10/04 06:44
MHDA- 2023/11/01 12:42
PMCR- 2023/09/25
CRDT- 2023/10/04 03:55
PHST- 2022/10/07 00:00 [received]
PHST- 2023/07/09 00:00 [revised]
PHST- 2023/08/01 00:00 [accepted]
PHST- 2023/11/01 12:42 [medline]
PHST- 2023/10/04 06:44 [pubmed]
PHST- 2023/10/04 03:55 [entrez]
PHST- 2023/09/25 00:00 [pmc-release]
AID - 10.1155/2023/3706421 [doi]
PST - epublish
SO  - Mediators Inflamm. 2023 Sep 25;2023:3706421. doi: 10.1155/2023/3706421. 
      eCollection 2023.