Matrix Degradation Research Articles

Diabetes mellitus exacerbates inflammation in a murine model of ligature-induced peri-implantitis: A histological and microtomographic study.

To investigate the influence of diabetes mellitus (DM) in a murine model of peri-implantitis (PI). Twenty-seven 4-week-old C57BL/6J male mice had their first and second maxillary left molars extracted. Eight weeks later, one machined implant was placed in each mouse. Four weeks after osseointegration, the mice were divided into three groups: (a) control (C), (b) PI and (c) DM + PI. DM was induced by streptozotocin (STZ) administration. After DM induction, PI was induced using ligatures for 2 weeks. The hemimaxillae were collected for micro-CT and histological analyses. The primary outcomes consisted of linear (mm) and volumetric (mm3) bone loss. Secondary outcomes were based on histological analysis and included inflammatory infiltrate, osteoclastic activity, matrix organization, composition and remodelling. Data are presented as means ± SEM. Statistical analyses were performed using one-way ANOVA, followed by Tukey's test. Gingival tissue oedema was detected in the PI and DM + PI groups. Micro-CT showed significantly increased linear and volumetric bone loss in the DM + PI group compared to the C and PI groups. H&E staining showed greater inflammatory response and bone resorption in the PI and DM + PI groups than in the C group. The DM + PI group had significantly higher osteoclast numbers than the C and PI groups. Picrosirius red stained less for types I and III collagen in the PI and DM + PI groups than in the C group. There was a significant increase in monocyte/macrophage (CD-11b) counts and matrix metalloproteinases (MMP-2 and MMP-8) marker levels and a significant decrease in the matrix metalloproteinases inhibition marker (TIMP-2) levels in the DM + PI group compared to the C and PI groups. DM exacerbates PI-induced soft-tissue inflammation, matrix degradation and bone loss.

Bacterial film-based degradable triboelectric nanogenerator for both contact and non-contact sensing

As an emerging environmentally friendly energy conversion device, degradable triboelectric nanogenerators (TENGs) play an important role in self-powered sensing, health care and human–machine interaction. However, traditional degradable materials used in TENGs often suffer from limited material sources and complex preparation processes, restricting large-scale production for widespread applications. Here, we propose a simple and efficient way to prepare degradable TENGs with inactivated bacterial film, taking advantage of wide source, self-proliferation and easy culture properties of bacteria. The prepared bacterial film-based TENG (BF-TENG) has stable electrical output, good durability and fatigue resistance, along with superior capabilities in both contact and non-contact sensing. In contact mode, the BF-TENG can generate a peak voltage of up to 83.3 V, which is employed for accurate Morse code transmission. In non-contact mode, the BF-TENG is capable of effectively perceiving the target polymer at a distance of 150 cm. The non-contact LED control circuit and a sensing array based on BF-TENG further demonstrate its practical potential for gesture recognition and spatial position perception. Furthermore, the fully degradable nature of BF-TENG ensures effortless disposal after use without environmental impact, serving as a promising solution for the new generation of eco-friendly and sustainable sensing devices.

M proteins of group A Streptococcus bind hyaluronic acid via arginine-arginine/serine-arginine motifs.

Tissue injury, including extracellular matrix (ECM) degradation, is a hallmark of group A Streptococcus (GAS) skin infection and is partially mediated by M proteins which possess lectin-like properties. Hyaluronic acid is a glycosaminoglycan enriched in the cutaneous ECM, yet an interaction with M proteins has yet to be explored. This study revealed that hyaluronic acid binding was conserved across phylogenetically diverse M proteins, mediated by RR/SR motifs predominantly localized in the C repeat region. Keratinocyte wound healing was decreased through the recruitment of hyaluronic acid by M proteins in an M type-specific manner. GAS strains 5448 (M1 serotype) and ALAB49 (M53 serotype) also bound hyaluronic acid via M proteins, but hyaluronic acid could increase bacterial adherence independently of M proteins. The identification of host-pathogen mechanisms that affect ECM composition and cell repair responses may facilitate the development of nonantibiotic therapeutics that arrest GAS disease progression in the skin.

Correlation of MMP-9 (Matrix Metalloproteinase 9) and SMA (Smooth Muscle Actin) expression with Basal Cell Carcinoma’s risk of recurrence

Basal Cell Carcinoma (BCC) is the most common cancer in many countries, with its incidence steadily rising. Data from the Indonesian Pathologists Association show that among 1,530 skin cancer cases, BCC was the most frequent (39.93%), followed by Squamous Cell Carcinoma (23%) and Malignant Melanoma (7.9%). According to the 2018 WHO classification, BCC is divided into Low-Risk and High-Risk groups based on the risk of recurrence. BCC invades surrounding tissues through extracellular matrix degradation and enhanced cell motility, driven by the expression of MMP-9 (Matrix Metalloproteinase 9) and SMA (Smooth Muscle Actin). This study aims to evaluate the expression of MMP-9 and SMA in BCC using immunohistochemistry and analyze their correlation with the risk of recurrence. A total of 40 paraffin blocks from BCC patients diagnosed between 2019 and 2021 at Dr. Saiful Anwar General Hospital in Malang, Indonesia, were sampled. The blocks were sectioned, stained with MMP-9 and SMA antibodies, and examined for positive expression indicated by brown staining in the cytoplasm of tumor cell and peritumoral stroma. Spearman correlation showed r = 0.811 for MMP-9 and r = 0.857 for SMA (p < 0.05, CI: 95%), indicating a significant relationship between these markers and the risk of recurrence. Higher MMP-9 and SMA expression corresponded to a higher risk of BCC recurrence, suggesting their potential as prognostic biomarkers. However, further research is needed to assess recurrence risk more accurately and determine the most appropriate therapy.

ТЕХНОЛОГИЯ ПОЛУЧЕНИЯ НАНОКАПСУЛ ДЛЯ ДОСТАВКИ ЛЕКАРСТВЕННЫХ СРЕДСТВ

Encapsulation of active ingredients in solid capsules made of biodegradable materials has attracted considerable attention over the past decades. In this brief review, we focus on the preparation of micro- and nanosized capsules and emulsions based on artificial peptides as a fully degradable material. It discusses various approaches to the preparation of polymer-based capsules as well as their critical properties such as size and stability. Dispersed polymer nanocapsules can serve as nanosized drug carriers to achieve controlled release as well as effective drug administration. The stability of the dispersion is determined by the type of surfactant and the nature of the outer shell of the capsule. Their release and degradation properties largely depend on the composition and structure of the capsule walls. Another important criterion is the capsule size, where the optimum is usually observed in the radius range of 100 to 500 nm. Nanocapsules can be prepared in fundamentally different ways: nanoprecipitation, emulsion diffusion, double emulsification, emulsion coacervation, polymer coating and layer-by-layer, and depend on the methodological and mechanistic aspects, encapsulation of the active substance and the raw materials used. Nanocapsules made using various biodegradable polymers are attracting increasing attention and are considered as one of the most promising drug delivery systems. Nanoencapsulated systems have a relatively higher intracellular absorption compared to microparticles, which can be modified depending on the surface charges of the nanocapsules and the hydrophilic or hydrophobic nature of the polymer used to form the shell.

Multiple ASC-dependent inflammasomes drive differential pro-inflammatory cytokine production in a mouse model of tendinopathy.

Inflammasomes are multiprotein complexes that regulate the bioactive production of IL-1b and IL-18, being implicated in the inflammatory response of different diseases. The inflammasome formed by the cytosolic sensor NLRP3 is highly promiscuous, as it could be activated by different pathogen- and sterile-signals. However, few models have studied the implication of NLRP3 in tissue damage-induced inflammation, particularly the implication of NLRP3 in tendinopathies. Here we aimed to investigate the implication of NLRP3 in a mouse model of tendinopathy by collagenase degradation of the extracellular matrix in the Achilles' mice tendon. We found that NLRP3 was involved in the production of IL-1b and IL-6, but another ASC-dependent inflammasome was required to produce IL-18 during sterile tissue damage. Our study suggests that in the immune response to extracellular matrix degradation different inflammasomes, probably expressed in different cell compartments, were able to differentially control IL-1b and IL-18 production in vivo. These results suggest the potential use of therapies targeting ASC as beneficial in the treatment of tendinopathies.

Structural variation of types IV-A1- and IV-A3-mediated CRISPR interference

CRISPR-Cas mediated DNA-interference typically relies on sequence-specific binding and nucleolytic degradation of foreign genetic material. Type IV-A CRISPR-Cas systems diverge from this general mechanism, using a nuclease-independent interference pathway to suppress gene expression for gene regulation and plasmid competition. To understand how the type IV-A system associated effector complex achieves this interference, we determine cryo-EM structures of two evolutionarily distinct type IV-A complexes (types IV-A1 and IV-A3) bound to cognate DNA-targets in the presence and absence of the type IV-A signature DinG effector helicase. The structures reveal how the effector complexes recognize the protospacer adjacent motif and target-strand DNA to form an R-loop structure. Additionally, we reveal differences between types IV-A1 and IV-A3 in DNA interactions and structural motifs that allow for in trans recruitment of DinG. Our study provides a detailed view of type IV-A mediated DNA-interference and presents a structural foundation for engineering type IV-A-based genome editing tools.

Xenon plasma-focused ion beam milling for fabrication of high-purity, bright single-photon sources operating in the C-band

Electron beam lithography is a standard method for fabricating photonic micro and nanostructures around semiconductor quantum dots (QDs), which are crucial for efficient single and indistinguishable photon sources in quantum information processing. However, this technique is difficult for direct 3D control of the structure shape, complicating the design and enlarging the 2D footprint to suppress in-plane photon leakage while directing photons into the collecting lens aperture. Here, we present an alternative approach to employ xenon plasma-focused ion beam (Xe-PFIB) technology as a reliable method for the 3D shaping of photonic structures containing low-density self-assembled InAs/InP quantum dots emitting in the C-band range of the 3rd telecommunication window. The method is optimized to minimize the possible ion-beam-induced material degradation, which allows exploration of both non-deterministic and deterministic fabrication approaches, resulting in photonic structures naturally shaped as truncated cones. As a demonstration, we fabricate mesas using a heterogeneously integrated structure with a QD membrane atop an aluminum mirror and silicon substrate. Finite-difference time-domain simulations show that the angled sidewalls significantly increase the emission collection efficiency to approx. 0.9 for NA = 0.65. We demonstrate experimentally a high purity of pulsed single-photon emission (∼99%) and a superior extraction efficiency value reported in the C-band of η = 24 ± 4%.

Development of Stable and Intensified Mixing Processes for the Precise and Scalable Production of Uniform Drug Delivery Nanocarriers.

Nanocarriers show great promise in drug delivery but face challenges in stability, uniformity, and morphology control. This work introduces an enhanced mixing process to overcome these obstacles, specifically aiming to produce consistently sized poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with anti-tumor drugs. By innovatively integrating a pulsation dampener into the microfluidic channels of a continuous flow preparation system, the flow stability of piston pumps is improved nearly tenfold. Consequently, large-scale production of uniformly sized nanoparticles with customizable dimensions is achieved through nanoprecipitation. Furthermore, incorporating terminal double-bond-functionalized poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-maleimide (PLGA-PEG-Mal) enables these nanoparticles to act as nano-crosslinkers. This facilitates in situ crosslinking with thiolated hyaluronic acid via a spontaneous thiol-ene coupling reaction under physiological conditions, allowing for minimally invasive drug administration and significantly enhancing localized drug retention. The material's degradability in the presence of endogenous enzymes ensures controlled drug release, as demonstrated with the anti-tumor drug doxorubicin (DOX). Validation in a murine breast cancer model shows reduced toxicity and a substantial reduction in tumor weight compared to the free DOX group. These findings confirm the approach's effectiveness for breast cancer treatment and pave the way for innovative solutions in nanomedicine, providing a practical microfluidic mixing system for the design and large-scale production of nanomedicines.

Empagliflozin treatment pre- and post- acute myocardial infarction reduces no-reflow, inflammatory cell infiltration and infarct size while preserving cardiac function.

Abstract Background and aims Empagliflozin (EMPA) and other members of the family of sodium glucose co-transporter 2 inhibitors have demonstrated clinical benefit in terms of survival and rehospitalizations in heart failure. However, their effect on acute myocardial infarction (AMI) is still under investigation. Microvascular injury (MVI) and no-reflow are major determinants of myocardial infarct size (IS) and prognosis. We investigated EMPA’s cardioprotective potential in AMI in terms of no-reflow, MVI and IS emphasizing on a translational regimen with EMPA treatment after AMI. Methods In a first series of experiments, C57Bl6 male mice (n=10 per group) were randomized into 1) Sham, 2) Control-AMI and 3) EMPA-Pre-AMI (10mg/kg/day orally for 6 weeks) groups. Mice underwent 30 min ischemia (I) and 2h reperfusion (R) or sham operation. Cell sorting and 3’ mRNA sequencing were applied to identify the cell types that are transcriptionally affected by EMPA pretreatment in mice with AMI. In a second series of experiments, the protocol was repeated, and an additional group was added, EMPA-Post-AMI (n=8-11 mice per group) in which oral treatment was performed 1h after R. Assessment of no-reflow via thioflavin S staining and electron microscopy was performed at 48 h. The infiltration of inflammatory cells in the ischemic heart was examined via flow cytometry. IS and myocardial function were determined by cardiac magnetic resonance (CMR). Type-2 diabetes mellitus patients received insulin (n=18) or EMPA (n=24) within 2 months post-AMI. Endothelial glycocalyx and endothelial-related circulating markers were examined at 4 months and 12 months post-AMI. Results EMPA pretreatment reversed AMI-induced alterations in cardiac endothelial cells’ (ECs) transcriptome. As such, it promoted the expression of survival genes, reduced gene expression related to adhesion molecules and ECs matrix degradation. Conversely, EMPA pretreatment exerted minimal effects on cardiomyocyte and fibroblast transcriptome. In support of the effect of EMPA on ECs, EMPA-Pre-AMI and EMPA-Post-AMI groups significantly reduced no-reflow and MVI as indicated by electron microscopy and histology at 48h of R. Moreover, both EMPA treatment pre-AMI and post-AMI reduced the infiltration of inflammatory monocytes and neutrophils in the infarcted myocardium suggesting enhanced vascular integrity. Both EMPA-Pre-AMI and EMPA-Post-AMI reduced IS and preserved cardiac function defined by CMR. Patients receiving EMPA presented with improved endothelial glycocalyx thickness, % global longitudinal strain and preserved pulse wave velocity. Conclusions EMPA treatment either before or after AMI protects against MVI, reduces no-reflow and IS and preserves cardiac function. Our data support the use of EMPA after recanalization in patients with AMI to confer improvement of cardiovascular function.

Inguinal hernia: a view from the 21st century (a review)

The proposed review is a look at the pathogenesis of inguinal hernia from the standpoint of molecular biology, as well as an attempt to understand the problems that are a consequence of explantation: issues of male fertility, chronic inflammation, carcinogenesis. It is proven that the pathogenesis of inguinal hernia is not reduced to a defect of the anterior abdominal wall. Moreover, the formation of this defect is preceded by a complex of modification of connective tissue components, which is based on the separation of the processes of extracellular matrix synthesis and matrix degradation with the predominance of the latter that disrupts the rotation of structures responsible for mechanical strength and elasticity. From this point of view, inguinal hernia is a multifactorial and heterogeneous disease.

Impact of Biofilms on Surface Properties of Polymethyl Methacrylate (PMMA) Resins.

Poly(methyl methacrylate) (PMMA) resins are widely used in medical and dental applications. Their susceptibility to bacterial biofilm formation poses significant challenges related to material degradation and infection risk. This study investigated the effects of Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) biofilms on PMMA resin surface properties over a 45-day period at 35°C. The study examined various parameters including biofilm adhesion, morphology, surface roughness, hydrophobicity, solid fraction, and zeta potential. PMMA resin specimens were inoculated with bacteria and incubated for 45 days. Biofilm adhesion was visually assessed, while surface characterization was conducted using scanning electron microscopy (SEM), atomic force microscopy (AFM), roughness analysis, contact angle measurements, solid fraction determination, and zeta potential analysis. The P. aeruginosa and S. aureus isolates were selected based on their biofilm-positive characteristics, which were further confirmed using Congo red and biofilm formation assays through crystal violet staining and spectrophotometric analysis. The results demonstrated robust biofilm adhesion on PMMA surfaces. SEM and AFM imaging revealed textured surfaces with elevated structures and depressions within the biofilm matrix. Biofilm-exposed resins exhibited significantly increased roughness (Ra = 164.5 nm, Rq = 169.5 nm) and hydrophobicity (mean angle = 85.5°-90.5°) compared to control samples (Ra = 38-50 nm, angle = 55°). Solid fraction measurements indicated a denser biofilm matrix on exposed resins (0.908) compared to controls (0.65). Additionally, zeta potential values were more negative for biofilm-exposed resins (mean = -84.2 mV) than controls (-45.0 mV). These findings underscore the substantial alterations in PMMA resin surface properties induced by bacterial biofilms, emphasizing the critical need for strategies to prevent biofilm formation and mitigate associated risks in healthcare settings. Future research should focus on developing anti-biofilm coatings or treatments to preserve the integrity and functionality of PMMA materials.

Evaluating the Photocatalytic Activity of Green Synthesized Iron Oxide Nanoparticles

Water pollution from dyes is a major environmental challenge, demanding advanced materials for efficient degradation. In this study, we synthesized iron oxide nanoparticles (IONPs) using an aqueous extract of Senegalia catechu leaves and evaluated their photocatalytic activity in methylene blue (MB) dye degradation under sunlight irradiation. The IONPs were characterized by UV-visible spectroscopy (UV–vis), Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray Spectroscopy (EDS). XRD pattern showed a highly crystalline structure with an average crystallite size of 34.7 nm, while SEM images revealed predominantly spherical particles with uneven surface texture. Photocatalytic efficiency exceeded 80% MB dye degradation after 120 min of sunlight exposure. Optimization of catalyst dose, pH, dye concentration, and other parameters is essential for maximizing degradation efficiency. The IONPs demonstrated reusability over four degradation cycles, retaining effective photocatalytic performance. This study underscores the potential of green-synthesized IONPs as eco-friendly photocatalysts for wastewater treatment and environmental remediation.

Upcycling waste polypropylene with basalt fibre reinforcement enhancing additive manufacturing feedstock for advanced mechanical performance

This research seeks to overcome the printing and processing challenges of using waste polypropylene (PP) reinforced with short basalt fibres, transforming them into upcycled feedstock for additive manufacturing. It introduces an optimised method for producing filaments and 3D printing with these materials, addressing common issues such as adhesion and warpage through innovative techniques while achieving maximum mechanical performance in the resulting composites. Basalt fibre weight fractions of 0 %, 2 %, 5 %, 8 %, 15 %, 30 %, and 50 % were used to reinforce the recycled polypropylene, improving both printability and mechanical properties. The tensile strength reached 53.58 MPa at 15 % fibre content, while the flexural strength peaked at 34.06 MPa with 30 % fibre content, revealing distinct interactions between the fibres and polymer under tensile and flexural loading that were not previously observed. Microstructure, voids, debonding, and dispersion were examined using optical and scanning electron microscopy. Differential Scanning Calorimetry (DSC) was performed to assess the thermal behaviour and crystallinity of the recycled polymer during filament production and printing, revealing slight matrix degradation during these processes. The findings highlight the potential of waste basalt fibre-reinforced PP as a valuable filament feedstock for 3D printing, supporting a circular economy approach to composite manufacturing.

Corrosion on cultural heritage buildings in Jordan in current situation and in future climate scenarios

This study examines the impact of air pollution on Jordan’s cultural heritage sites, focusing on key pollutants (SO2, HNO3, O3, PM10) and climate conditions. Using 2019 data and future projections for 2040–2059 and 2080–2099, the research reveals significant material corrosion in urban areas like Amman and Irbid, driven by pollutants such as SO₂ and PM10. Random Forest Analysis identifies these pollutants as primary contributors to material degradation. Future scenarios indicate corrosion rates exceeding safe limits across Jordan, underscoring the need for proactive conservation strategies. This work highlights the critical role of air quality management in protecting cultural heritage, especially under climate change pressures, and provides guidance for national policy development.

Recruitment of autophagy initiator TAX1BP1 advances aggrephagy from cargo collection to sequestration.

Autophagy mediates the degradation of harmful material within lysosomes. In aggrephagy, the pathway mediating the degradation of aggregated, ubiquitinated proteins, this cargo material is collected in larger condensates prior to its sequestration by autophagosomes. In this process, theautophagic cargo receptors SQSTM1/p62 and NBR1 drive cargo condensation, while TAX1BP1, which binds to NBR1, recruits the autophagy machinery to facilitate autophagosome biogenesis at the condensates. The mechanistic basis for the TAX1BP1-mediated switch from cargo collection to its sequestration is unclear. Here we show that TAX1BP1 is not a constitutive component of the condensates. Its recruitment correlates with the induction of autophagosome biogenesis. TAX1BP1 is sufficient to recruit the TBK1 kinase via the SINTBAD adapter. We define the NBR1-TAX1BP1-binding site, which is adjacent to the GABARAP/LC3 interaction site, and demonstrate that the recruitment of TAX1BP1 to cargo mimetics can be enhanced by an increased ubiquitin load. Our study suggests that autophagosome biogenesis is initiated once sufficient cargo is collected in the condensates.

Influence of Oligomeric Lactic Acid and Structural Design on Biodegradation and Absorption of PLA-PHB Blends for Tissue Engineering

The advancing development in biomaterials and biology has enabled the extension of 3D printing technology to the bioadditive manufacturing of degradable hard tissue substitutes. One of the key advantages of bioadditive manufacturing is that it has much smaller design limitations than conventional manufacturing and is therefore capable of producing implants with complex geometries. In this study, three distinct blends of polylactic acid (PLA) and polyhydroxybutyrate (PHB) were produced using Fused Deposition Modeling (FDM) technology. Two of these blends were plasticized with oligomeric lactic acid (OLA) at concentrations of 5 wt% and 10 wt%, while the third blend remained unplasticized. Each blend was fabricated in two structural modifications: solid and porous. The biodegradation behavior of the produced specimens was examined through an in vitro experiment using three different immersion solutions: saline solution, Hank’s balanced salt solution (HBSS), and phosphate-buffered saline (PBS). All examined samples were also subjected to chemical analysis: atomic absorption spectroscopy (AAS), scanning electron microscopy (SEM), and energy-dispersive spectrometry (EDS). The results of the degradation experiments indicated a predominantly better absorption capacity of the samples with a porous structure compared to the full structure. At the same time, the blend containing a higher concentration of OLA exhibited enhanced pH stability over the evaluation period, maintaining relatively constant pH values before experiencing a minor decline at the end of the study. This observation indicates that the increased presence of the plasticizer may provide a buffering effect, effectively mitigating the acidification associated with material degradation.

Expression of Markers Associated with Epithelial-Mesenchymal Transition and Extracellular Matrix Degradation in Human Uveal Melanoma.

The expression of markers associated with epithelial-mesenchymal transition (EMT) and extracellular matrix degradation in human uveal melanoma tissue samples and postequatorial zone of the choroid was assessed by immunohistochemical staining. Increased expression of EMT markers E-cadherin and vimentin was observed in the tumor. The ratio of MMP-9 to TIMP-1 proteins related to the extracellular matrix degradation was higher in the tumor. These results may indicate activation of EMT-like process in the uveal melanoma cells and degradation of the extracellular matrix, which can contribute to the development of collective invasion in uveal melanoma.

Parametric identification of coefficients for a model of fatigue stiffness degradation of a composite material

The problem of finding the fatigue characteristics of a composite material based on test results is considered. The results of endurance tests of unidirectional polymer composite materials with different initial stiffness, breaking stress and working cycle stress were used as the initial data. As a mathematical model of stiffness degradation, a nonlinear ordinary differential equation with five unknown parameters is used, reflecting characteristic changes in the properties of the material. It is required to find such parameter values that the solution of the differential equation should describe the available test results with sufficient accuracy. The solution procedure is reduced to the problem of optimizing the objective function, the value of which characterizes the achieved accuracy. As optimization methods, a method simulating the behavior of a flock of moths and a method of sequential reduction of the search set were used. A step-by-step algorithm for finding unknown model parameters is proposed, and numerical results of processing input data containing information on changing the elasticity modulus of the composite material in the course of applying load cycles are presented.

Elevated Netrin-4 Expression and Its Action in Infrapatellar Fat Pad

Knee osteoarthritis (KOA) is a degenerative joint disease characterized by inflammation and cartilage degradation. The infrapatellar fat pad (IFP), located beneath the patella within the knee joint, serves as a key anatomical structure involved in cushioning and supporting the knee. It is also an active endocrine organ that secretes various bioactive substances, potentially influencing the local inflammatory environment and contributing to KOA pathogenesis. Netrin-4 (NTN4), a protein primarily known for its role in neuronal guidance, has been implicated in various non-neuronal functions, including inflammatory processes and tissue remodeling. This study aims to explore the involvement of NTN4 in KOA, focusing on its expression in the IFP and its potential impact on disease progression. This study involved 82 patients with radiographically confirmed KOA undergoing total knee arthroplasty (TKA). The correlation between NTN4 expression and OA pathology, including Kellgren–Lawrence (K/L) grades, was investigated. NTN4-expressing cells were identified in the stromal vascular fraction, including fibroblastic, hematopoietic, and endothelial cells of the IFP. To elucidate the molecular effects of NTN4, RNA sequencing (RNA-seq) was performed on fibroblastic cells treated with recombinant NTN4. Subsequent quantitative PCR (qPCR) was used to validate the RNA-seq findings. NTN4 expression was significantly elevated in the IFP of patients with advanced KOA (K/L grades 3 and 4) compared to those with early-stage disease (K/L grade 2). Higher NTN4 expression was found in fibroblastic cells, and RNA-seq analysis revealed upregulation of genes associated with pro-inflammatory pathways, including IL-17 and TNF-α signaling, and matrix degradation. Notably, genes including IL6, MMP1, CXCL1, and CXCL8 were significantly elevated, as confirmed by qPCR, indicating NTN4’s role in promoting an inflammatory and catabolic environment. Our findings suggest that NTN4 plays a significant role in the pathogenesis of KOA by promoting inflammation and matrix degradation within the IFP. Although NTN4 expression was not directly correlated with clinical symptoms, its elevated expression in fibroblastic cells and influence on inflammatory and degradative pathways suggest a potential mechanism for exacerbating joint damage. Targeting NTN4 could offer a novel therapeutic approach to mitigating inflammation and slowing disease progression in KOA, ultimately improving patient outcomes. Further research is needed to clarify NTN4’s specific roles and therapeutic potential in OA management.