Biology subjects

Marahleh, A.

Publications and source records attributed to Marahleh, A..

3 recordsLinked to original sources

bioRxiv2025

Rewiring of RNA-protein coupling in osteocytes in response to hyperglycemic levels of glucose

Osteocytes are central regulators of skeletal homeostasis, yet how their transcriptome and proteome jointly adapt to metabolic stress is unclear. Here, we combined RNA-sequencing with label-free quantitative proteomics in MLO-Y4 osteocytic cells exposed to hyperglycemic levels of glucose, to interrogate RNA-protein coupling at baseline and under hyperglycemic stress. Transcriptionally, high glucose and mannitol elicited overlapping osmoadaptive transcriptional programs indicative of metabolic remodeling, whereas high glucose alone induced mitochondrial and oxidative phosphorylation downregulation alongside selective activation of bone anabolic and inflammatory pathways. RNA-protein integration revealed moderate coupling at baseline, indicating that mRNA levels capture only part of the proteomic output. High glucose reorganized RNA-protein relationship, sorting genes into four patterns of matched or opposing RNA-protein responses. The four groups were enriched in distinct biological pathways that shaped cellular response to stress exposing significant post-transcriptional and translational control under high glucose levels. These data indicate that osteocytes adapt to stress through program-specific RNA-protein interactions in which post-transcriptional regulation of protein translation reshapes the proteome beyond what is predicted by mRNA levels.

bioinformatics↗

bioRxiv2025

The RNA-Binding Protein HuR Regulates Splicing Programs in Osteocytes

Post-transcriptional gene regulation is central to maintaining cellular homeostasis, among its mechanism alternative splicing (AS) fine-tunes cellular adaptation to stress. In this study we employed an approach combining RNA splicing analysis to define RNA binding protein (RBP) motif enrichment around alternatively spliced exons in primary osteocytes cultured in high glucose conditions (HG). We identified the RBP human antigen R (HuR) as a top candidate regulator of AS. Loss of HuR reshaped the transcriptome through widespread changes in gene expression and splicing, converging on two major pathways: stress response and translational control. Functional validation of splicing revealed that HuR depletion heightened oxidative stress sensitivity and compromised cell viability under HG by stabilizing and upregulating TXNIP, a thioredoxin inhibitor. HuR knockdown also impaired mitochondrial mass and function and disrupted key translational signals, despite preserving global protein output. These findings establish HuR as a central post-transcriptional regulator of osteocyte survival and metabolic adaptation under high glucose stress, with potential implications for hyperglycemic bone fragility.

molecular biology↗

bioRxiv2019

Establishment of an orthodontic retention mouse model and the effect of anti-c-Fms antibody on orthodontic relapse

Orthodontic relapse after orthodontic treatment is a major clinical issue in the dental field. However, the biological mechanism of orthodontic relapse is still unclear. This study aimed to establish a mouse model of orthodontic retention to examine how retention affects the rate and the amount of orthodontic relapse. We also sought to examine the role of osteoclastogenesis in relapse using an antibody to block the activity of M-CSF, an essential factor of osteoclast formation. Mice were treated with a nickel-titanium closed-coil spring that was fixed between the upper incisors and the upper-left first molar to move the first molar in a mesial direction over 12 days. Mice were randomly divided into three groups: group 1, no retention (G1); group 2, retention for 2 weeks (G2); and group 3, retention for 4 weeks (G3). In G2 and G3, a light-cured resin was placed in the space between the first and second molars as a model of retention. Orthodontic relapse was assessed by measuring changes in the dimensions of the gap created between the first and second molars. To assess the activity and role of osteoclasts, mice in G3 were injected with anti-c-Fms antibody or PBS, and assessed for changes in relapse distance and rate. Overall, we found that a longer retention period was associated with a slower rate of relapse and a shorter overall amount of relapse. In addition, inhibiting osteoclast formation using the anti-c-Fms antibody also reduced orthodontic relapse. These results suggest that M-CSF and/or its receptor could be potential therapeutic targets in the prevention and treatment of orthodontic relapse.

immunology↗