BNTA attenuates temporomandibular joint osteoarthritis progression by directly targeting ALDH3A1: An in vivo and in vitro study

Kaixun He; Hanyu Lin; Sihui Zhang; Yanjing Ou; Jie Lu; Wenqian Chen; Yuwei Zhou; Yang Li; Yanjun Lin; Jingjing Su; Yifeng Xing; Huachen Chen; Jiang Chen

doi:10.1016/j.intimp.2023.110963

BNTA attenuates temporomandibular joint osteoarthritis progression by directly targeting ALDH3A1: An in vivo and in vitro study

Int Immunopharmacol. 2023 Nov;124(Pt B):110963. doi: 10.1016/j.intimp.2023.110963. Epub 2023 Sep 21.

Authors

Kaixun He¹, Hanyu Lin¹, Sihui Zhang¹, Yanjing Ou¹, Jie Lu², Wenqian Chen², Yuwei Zhou², Yang Li², Yanjun Lin¹, Jingjing Su², Yifeng Xing², Huachen Chen², Jiang Chen³

Affiliations

¹ Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian 350002, PR China; Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian 350002, PR China.
² Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian 350002, PR China.
³ Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key Lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian 350002, PR China; Institute of Stomatology & Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian 350002, PR China. Electronic address: jiangchen@fjmu.edu.cn.

PMID: 37741125
DOI: 10.1016/j.intimp.2023.110963

Abstract

BNTA is known to have a therapeutic effect on knee osteoarthritis and inflammatory osteoclastogenesis. However, the protective effect of BNTA regarding temporomandibular mandibular joint osteoarthritis (TMJOA) and its underlying mechanism and physiological target remains unclear. In the present study, BNTA ameliorated cartilage degradation and inflammation responses in monosodium iodoacetate (MIA)-induced TMJOA in vivo. In IL-1β-induced condylar chondrocytes, BNTA prevents oxidative stress, inflammatory responses and increasing synthesis of cartilage extracellular matrix through activating nuclear factor-E2-related factor 2 (NRF2) signaling. Suppression of NRF2 signaling abolishes the protective effect of BNTA in TMJOA. Notably, BNTA may bind directly to ALDH3A1 and act as a stabilizer, as evidenced by drug affinity responsive target stability assay (DARTS), cellular thermal shift assay (CETSA) and molecular docking results. Further investigation of the underlying molecular and cellular mechanism infers a positive correlation of ALDH3A1 regulating NRF2 signaling. In conclusion, BNTA may attenuate TMJOA progression via the ALDH3A1/NRF2 axis, inferring that BNTA is a therapeutic target for treating temporomandibular mandibular joint osteoarthritis.

Keywords: ALDH3A1; BNTA; NRF2; Small molecule; Temporomandibular joint osteoarthritis.

MeSH terms

Aldehyde Dehydrogenase / metabolism
Cartilage / metabolism
Chondrocytes
Humans
Molecular Docking Simulation
NF-E2-Related Factor 2* / metabolism
Osteoarthritis* / metabolism
Temporomandibular Joint

Substances

NF-E2-Related Factor 2
ALDH3A1 protein, human
Aldehyde Dehydrogenase