Histone deacetylase inhibitors attenuated interleukin-1β-induced chondrogenesis inhibition in synovium-derived mesenchymal stem cells of the temporomandibular joint

Bone & Joint Research

article

Wen-ting Liao¹  Jia-dong Sun¹  Yun Wang¹  Yi-qing He¹  Kai Su¹  Yun-yang Lu¹  Guiqing Liao¹  Yang-peng Sun¹ 

[1] Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology

关键词: Histone deacetylase inhibitors;    Temporomandibular joint;    Synovium;    Mesenchymal stem cell;    IL-1β;    synovium-derived mesenchymal stem cells;    temporomandibular joint;    chondrogenesis;    interleukin-1β;    IL-6;    matrix metalloproteinase 13;    Cartilage;    mouse model;    arthritis;    condylar cartilage;   

DOI  :  10.1302/2046-3758.111.BJR-2021-0059.R1

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsIn the repair of condylar cartilage injury, synovium-derived mesenchymal stem cells (SMSCs) migrate to an injured site and differentiate into cartilage. This study aimed to confirm that histone deacetylase (HDAC) inhibitors, which alleviate arthritis, can improve chondrogenesis inhibited by IL-1β, and to explore its mechanism.MethodsSMSCs were isolated from synovium specimens of patients undergoing temporomandibular joint (TMJ) surgery. Chondrogenic differentiation potential of SMSCs was evaluated in vitro in the control, IL-1β stimulation, and IL-1β stimulation with HDAC inhibitors groups. The effect of HDAC inhibitors on the synovium and condylar cartilage in a rat TMJ arthritis model was evaluated.ResultsInterleukin (IL)-1β inhibited the chondrogenic differentiation potential of SMSCs, while the HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and panobinostat (LBH589), attenuated inhibition of IL-1β-induced SMSC chondrogenesis. Additionally, SAHA attenuated the destruction of condylar cartilage in rat TMJ arthritis model. IL-6 (p < 0.001) and matrix metalloproteinase 13 (MMP13) (p = 0.006) were significantly upregulated after IL-1β stimulation, while SAHA and LBH589 attenuated IL-6 and MMP13 expression, which was upregulated by IL-1β in vitro. Silencing of IL-6 significantly downregulated MMP13 expression and attenuated IL-1β-induced chondrogenesis inhibition of SMSCs.ConclusionHDAC inhibitors SAHA and LBH589 attenuated chondrogenesis inhibition of SMSC induced by IL-1β in TMJ, and inhibition of IL-6/MMP13 pathway activation contributes to this biological progress. This study provides a theoretical basis for the application of HDAC inhibitors in the treatment of TMJ arthritis.

【 授权许可】

CC BY-NC