TY - JOUR
AB - High mobility group box 1 (HMGB1) is an important downstream product of pyroptosis in macrophages, and it serves a vital role in numerous inflammatory diseases. Previous studies have reported that HMGB1 is released by fibroblast‑like synoviocytes (FLSs) that are activated by inflammatory cytokines in knee osteoarthritis (KOA); however, the mechanism via which FLS promotes HMGB1 secretion in KOA remains unknown. According to our previous study, pyroptosis occurs in FLSs of patients with KOA and is mediated by Nod‑like receptor protein (NLRP)1 or NLRP3 inflammasomes. However, the specific relationship between HMGB1 secretion and FLS pyroptosis requires further investigation. In the present study, the association between HMGB1 secretion and FLS pyroptosis was investigated in vitro and in vivo. In this study, western blotting, ELISA and reverse transcription‑quantitative PCR were used to measure expression levels of proteins and mRNA. Caspase‑1 activity assay and Hoechst 33342/PI double staining were used to observe the pyroptosis of FLSs. Hematoxylin and eosin staining was used to observe the destruction of cartilage in KOA. Increased expression levels of pyroptosis‑related proteins and HMGB1 in the synovium of rat anterior cruciate ligament transection‑induced KOA models were identified, and these changes were significantly mitigated via the intra‑articular injection of a caspase‑1 inhibitor. In vitro, FLSs were treated with lipopolysaccharide (LPS) + ATP to induce pyroptosis, and HMGB1 secretion was subsequently measured. LPS + ATP significantly increased the expression levels of pyroptosis‑related proteins and HMGB1 in FLSs, and these effects were significantly mitigated by small interfering RNAs targeting NLRP1, NLRP3, apoptosis‑associated speck‑like protein with a caspase‑recruitment domain or caspase‑1. Therefore, the present results indicated that NLRP1/NLRP3 inflammasome‑mediated and caspase‑1‑dependent FLS pyroptosis increased HMGB1 secretion in KOA. These findings may provide a therapeutic strategy to decrease synovial inflammatory responses during KOA progression.
AD - Department of Orthopedics, Liyang Hospital of Traditional Chinese Medicine, Liyang, Jiangsu 213300, P.R. China
Department of Orthopedics, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China
Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
AU - Xiao,Yancheng
AU - Ding,Liang
AU - Yin,Songjiang
AU - Huang,Zhengquan
AU - Zhang,Li
AU - Mei,Wei
AU - Wu,Peng
AU - Wang,Peimin
AU - Pan,Ke
DA - 2021/02/01
DO - 10.3892/mmr.2020.11736
IS - 2
JO - Mol Med Rep
KW - KOA
FLS
pyroptosis
HMGB1
PY - 2021
SN - 1791-2997
1791-3004
SP - 97
ST - Relationship between the pyroptosis of fibroblast‑like synoviocytes and HMGB1 secretion in knee osteoarthritis
T2 - Molecular Medicine Reports
TI - Relationship between the pyroptosis of fibroblast‑like synoviocytes and HMGB1 secretion in knee osteoarthritis
UR - https://doi.org/10.3892/mmr.2020.11736
VL - 23
ER -