The bone tissue is a dynamic complex that constitutes of several interdependent systems and is continuously remodeled through the concerted actions of bone cells. Osteoblasts are mononucleated cells, derived from mesenchymal stem cells, responsible for bone formation. Osteoclasts are large multinucleated cells that differentiate from hematopoietic progenitors of the myeloid lineage and are responsible for bone resorption. The lineage-specific differentiation of bone cells requires an epigenetic regulation of gene expressions involving chromatin dynamics. The key step for understanding gene regulatory networks during bone cell development lies in characterizing the chromatin modifying enzymes responsible for reorganizing and potentiating particular chromatin structure. This review covers the histone-modifying enzymes involved in bone development, discusses the impact of enzymes on gene expression, and provides future directions and clinical significance in this area.

Peroxiredoxin 1 (PRDX1), an intracellular antioxidant enzyme, has emerged as a regulator of inflammatory responses via Toll-like receptor 4 (TLR4) signaling. Despite this, the mechanistic details of the PRDX1-TLR4 axis and its impact on osteoclast differentiation remain elusive. Here, we show that PRDX1 suppresses RANKL-induced osteoclast differentiation. Utilizing pharmacological inhibitors, we reveal that PRDX1 inhibits osteoclastogenesis through both TLR4/TRIF and TLR4/MyD88 pathways. Transcriptome analysis revealed PRDX1-mediated alterations in gene expression, particularly upregulating serum amyloid A3 (Saa3) and aconitate decarboxylase 1 (Acod1). Mechanistically, PRDX1-TLR4 signaling activates p65, promoting Saa3 and Acod1 expression while inhibiting Nfatc1, a master regulator of osteoclastogenesis. Remarkably, PRDX1 redirects p65 binding from Nfatc1 to Saa3 and Acod1 promoters, thereby suppressing osteoclast formation. Structural analysis showed that a monomeric PRDX1 mutant with enhanced TLR4 binding exhibited the potent inhibition of osteoclast differentiation. These findings reveal the PRDX1-TLR4 axis’s role in inhibiting osteoclastogenesis, offering potential therapeutic insights for bone disorders.

Bacterial pathogens have evolved sophisticated strategies to manipulate host cellular processes, ensuring survival, replication, and long-term persistence. Beyond classical immune signaling, emerging evidence highlights the central role of epigenetic regulation in host-pathogen interactions. Pathogens exploit host chromatin through 2 principal mechanisms: (1) direct modification of histones by bacterial effector proteins with intrinsic enzymatic activities and (2) indirect modulation of host epigenetic states through alterations in signaling pathways or cellular metabolism. These interventions alter post-translational histone modifications-acetylation, methylation, phosphorylation, and lactylation-thereby reshaping transcriptional programs to suppress antimicrobial responses, promote immune tolerance, or establish persistent infection. This review summarizes recent advances in understanding the dynamic interplay between bacterial virulence and host chromatin regulation, highlighting epigenetic reprogramming as a key determinant of infection outcomes.

Journal of Biomedical and Translational Research

Seokchan Lee, Jisu Lee, Sun-Ju Yi & Kyunghwan Kim. BMB Reports 2026;59:169-75. https://doi.org/10.5483/BMBRep.2025-0178

Osteoclastogenesis is driven by tightly coordinated transcriptional programs downstream of receptor activator of nuclear factor-κB ligand (RANKL) signaling, in which reactive oxygen species (ROS) function as essential secondary messengers. Although extracellular peroxiredoxin 1 (PRDX1) has been implicated in the suppression of osteoclast differentiation, the role of intracellular PRDX1 in regulating osteoclastogenic signaling remains poorly understood. Here, we identify intracellular PRDX1 as a redox-sensitive negative regulator of osteoclastogenesis and bone resorption. PRDX1 deficiency markedly enhanced osteoclast differentiation, bone resorption activity, and osteoporotic phenotypes in vivo. Transcriptomic and mechanistic analyses revealed that PRDX1 attenuates osteoclastogenic gene transcription by blocking the nuclear factor kappa B (NF-κB)/p65 signaling axis. Loss of PRDX1 increased intracellular ROS accumulation, promoted p65 nuclear translocation and promoter occupancy, thereby amplifying osteoclastogenic transcriptional programs. Mechanistically, PRDX1 underwent TNF receptor associated factor 6 (TRAF6)-mediated Lys67-dependent ubiquitylation and lysosomal degradation in response to RANKL signaling. In addition, RANKL-induced Src activation promoted phosphorylation of PRDX1 at Tyr194, which enhanced TRAF6-mediated ubiquitylation without substantially altering overall TRAF6 binding. Together, these findings reveal a PRDX1–ROS feedback loop that modulates NF-κB activity during osteoclastogenesis and identify regulated PRDX1 degradation as a mechanism by which RANKL signaling amplifies osteoclastogenic responses. These findings establish intracellular PRDX1 as an important modulator of skeletal homeostasis, suggesting its potential relevance as a pharmacological target in diseases characterized by excessive bone resorption.