Biology subjects

Vaes, N.

Publications and source records attributed to Vaes, N..

3 recordsLinked to original sources

bioRxiv2026

Interplay between canonical Wnt signaling and α5β1 integrins modulates mechanoresponse in human articular cartilage

ObjectivesMechanical cues are essential for maintaining cartilage function, yet how they integrate with molecular pathways dysregulated in osteoarthritis (OA) remains poorly defined in human tissue. Canonical Wnt signalling influences cartilage biology and cell-matrix interactions, but its role in integrin-dependent mechanoregulation in human cartilage is not fully understood. This study aimed to determine how Wnt activation affects chondrocyte responses to physiological mechanical loading, with a focus on 5{beta}1integrin and cytoskeletal organisation. MethodsHuman cartilage explants from non-OA and OA donors were subjected to short-term physiological cyclic compression. Canonical Wnt signalling was activated with CHIR99021, and integrin-mediated adhesion was modulated using the 5{beta}1 blocking peptide ATN-161 during loading. Chondrocyte responses were assessed by analysing mechanoresponsive and matrix-related gene expression, 5{beta}1 complex formation via proximity ligation assay and actin cytoskeletal organisation by confocal microscopy. ResultsOA chondrocytes exhibited a distinct integrin profile, characterised by increased ITGA5 and ITGB1 but reduced ITGA10 expression. In non-OA cartilage, canonical Wnt activation increased ITGB1 expression and 5{beta}1 integrin complex formation, while mechanical loading further enhanced ITGA5 and ITGB1 transcription under Wnt-activated conditions. Under control conditions, loading induced mechanoresponsive and anabolic gene expression in non-OA cartilage; these responses were attenuated following Wnt-activation and partially restored by 5{beta}1 blockade. Mechanical loading induced F-actin reorganization toward a more cortical distribution across cartilage zones, irrespective of disease status or treatment. Wnt activation did not result in distinct cytoskeletal phenotypes under load, and load-induced actin remodelling was comparable between groups. ConclusionThese findings identify 5{beta}1integrin as a key mediator linking canonical Wnt signalling to altered chondrocyte mechanoresponsiveness in human cartilage. While mechanical loading consistently induced cortical F-actin reorganization, Wnt-associated changes in load responsiveness arose primarily from integrin-dependent mechanisms rather than major alterations in actin organization. This study highlights the complexity of cartilage mechanoregulation and identifies integrin-mediated signaling as important contributors to canonical Wnt-driven alterations in load responsiveness relevant to OA.

molecular biology↗

bioRxiv2026

Adrenergic signaling induces a pro-tumorigenic B cell state in colorectal cancer

The importance of neuron-tumor crosstalk has gained increasing attention, yet its influence on the cellular and molecular landscape of colorectal cancer (CRC) remains largely unexplored. Here, we show that colonic innervation shapes the tumor immune microenvironment in a murine model of colitis-associated CRC. Although neuronal density does not affect tumor number, size, or overall burden, transcriptomic profiling of cells isolated from the tumor of hypo-innervated mice revealed extensive differential gene expression, including genes involved in immunoglobulin (Ig) signaling and the cancer-relevant hallmark avoiding immune destruction. Flow cytometry analysis of leukocyte populations demonstrated a significant reduction of B cells in the cancerous colon of hypo-innervated mice, notably a decrease in germinal center B cells and an altered class-switching profile, characterized by reduced IgA and increased IgD expression. Fluorescence and transmission electron microscopy showed that colonic B cells are primarily localized in the submucosa near neuronal processes containing varicose release sites, suggesting direct neuron-B cell interactions. Functional assays revealed that adrenergic stimulation of B cells promotes their proliferation and maturation, enhances IL-10 secretion, and alters immunoglobulin profiles. Strikingly, the transcriptome of epinephrine-treated B cells closely mirrors that of plasma cells from human CRC tissues, and the transcriptomic signature of these epinephrine-stimulated B cells associates with poorer patient survival. Together, these findings uncover an adrenergic neuron - B cell axis in CRC, providing evidence for direct neuroimmune interactions that affect B cell maturation and may influence tumor progression and therapeutic responses.

cancer biology↗

bioRxiv2025

Osteoarthritis leads to more contractile and protrusive chondrocytes when cultured in 3D degradable hydrogels

Osteoarthritis (OA) induces phenotypic changes in chondrocytes as well as alterations in matrix composition and mechanics. Yet, its impact on active cell-generated forces, a key indicator of cell-matrix interaction, remains poorly characterized. In this study, we systematically compared the force generation capacity and associated proteins of interest between human OA and non-OA articular chondrocytes and how they are affected by cell culture dimensionality (2D versus 3D) and matrix degradability. Using traction force microscopy (TFM) combined with high-resolution immunostainings we show that OA alters the expression and organization of proteins involved in force exertion and transmission across both 2D and 3D cultures, but only in a 3D degradable hydrogel environment do these changes translate into higher cell-generated contractile forces This increased force generation correlates with elevated protrusive activity, higher actomyosin content and engagement, as well as altered localization of adhesion and matrix proteins, all of which could contribute to increased cell-matrix interaction in OA chondrocytes. In contrast, OA chondrocytes display no increase in cell tractions when cultured on 2D hydrogel substrates. These findings demonstrate that the detection and interpretation of OA-related alterations in chondrocyte mechanobiology are strongly dependent on the dimensionality and degradable properties of the culture system. Our results highlight the critical role of 3D degradable environments in revealing disease-associated changes in chondrocyte force generation and emphasize the necessity of carefully selecting model systems when investigating OA mechanobiology.

bioengineering↗