MTHFD2 promotes osteoclastogenesis and bone loss in rheumatoid arthritis by enhancing CKMT1-mediated oxidative phosphorylation.

ABSTRACT:

Background

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by disrupted bone homeostasis. This study investigated the effect and underlying mechanisms of one-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) on osteoclast differentiation and bone loss in RA.

Methods

The expression of MTHFD2 was examined in CD14 + monocytes and murine bone marrow-derived macrophages (BMMs). RNA-sequencing was performed to evaluate the regulatory mechanisms of MTHFD2 on osteoclastogenesis. Extracellular flux assay, JC-1 staining, and transmission electron microscopy were used to detect mitochondrial function and energy metabolism changes during osteoclast formation. Collagen-induced arthritis (CIA) mice were used to evaluate the therapeutic eff

SUBMITTER: Li Y 

PROVIDER: S-EPMC11866863 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature