Student and Faculty Publications
Publication Date
8-1-2023
Journal
Redox Biology
Abstract
TMBIM6 is an endoplasmic reticulum (ER) protein that modulates various physiological and pathological processes, including metabolism and cancer. However, its involvement in bone remodeling has not been investigated. In this study, we demonstrate that TMBIM6 serves as a crucial negative regulator of osteoclast differentiation, a process essential for bone remodeling. Our investigation of Tmbim6-knockout mice revealed an osteoporotic phenotype, and knockdown of Tmbim6 inhibited the formation of multinucleated tartrate-resistant acid phosphatase-positive cells, which are characteristic of osteoclasts. Transcriptome and immunoblot analyses uncovered that TMBIM6 exerts its inhibitory effect on osteoclastogenesis by scavenging reactive oxygen species and preventing p65 nuclear localization. Additionally, TMBIM6 depletion was found to promote p65 localization to osteoclast-related gene promoters. Notably, treatment with N-acetyl cysteine, an antioxidant, impeded the osteoclastogenesis induced by TMBIM6-depleted cells, supporting the role of TMBIM6 in redox regulation. Furthermore, we discovered that TMBIM6 controls redox regulation via NRF2 signaling pathways. Our findings establish TMBIM6 as a critical regulator of osteoclastogenesis and suggest its potential as a therapeutic target for the treatment of osteoporosis.
Keywords
Animals, Male, Mice, Bone Resorption, Cell Differentiation, Membrane Proteins, Mice, Inbred C57BL, Mice, Knockout, Osteoclasts, Osteogenesis, RANK Ligand, Signal Transduction, Transcription Factor RelA, Oxidation-Reduction, TMBIM6, Bone development, Osteoclastogenesis, Reactive oxygen species, p65
Included in
Bioinformatics Commons, Biology Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons
Comments
This article has been corrected. See Redox Biol. 2023 October; 66: 102844.
Supplementary Materials
Data Availability Statement
PMID: 37399733