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Topic:Extracellular matrix
The extracellular matrix (ECM) in horses is a complex network of proteins and polysaccharides that provides structural and biochemical support to surrounding cells. It is a dynamic entity involved in various physiological processes, including tissue repair, development, and homeostasis. In equine biology, the ECM is composed of components such as collagen, elastin, proteoglycans, and glycoproteins, which contribute to the integrity and functionality of tissues like cartilage, tendons, and skin. Alterations in the ECM can influence cellular behavior and are associated with conditions such as osteoarthritis and tendon injuries. This page aggregates peer-reviewed research studies and scholarly articles that explore the composition, function, and implications of the extracellular matrix in equine health and disease.
Alpha-2-Macroglobulin-Enriched Plasma Modulates Inflammatory and Proteolytic Pathways in Experimental Equine Musculoskeletal Models. Joint inflammation and extracellular matrix degradation are major contributors to the development of equine osteoarthritis and reduced athletic performance. Alpha-2-macroglobulin is a naturally occurring broad-spectrum inhibitor of proteases and inflammatory mediators that has emerged as a promising orthobiologic therapy. This study investigated the anti-inflammatory and matrix-protective effects of alpha-2-macroglobulin-enriched plasma in complementary in vitro and ex vivo equine models. Primary equine chondrocytes and synoviocytes isolated from healthy horses were stimulated with interleukin...
Conserved skeletal muscle transcriptomic responses to pacing strategies in Thoroughbred horses. This study investigated whether different pacing patterns during high-intensity exercise elicit distinct transcriptional responses in equine skeletal muscle. Eight Thoroughbred horses completed two treadmill exercise sessions in a randomized crossover design. In the positive-pacing condition, horses exercised at 110% maximal O₂ uptake (V˙O₂max) for 1 min followed by 90% V˙O₂max for 1 min, whereas in the negative-pacing condition, the order was reversed. At 4 h after exercise, the positive-pacing protocol resulted in upregulation of 1,989 genes and downregulation of 840 genes, whereas t...
Interleukin 12 on extracellular matrix-related factors and functional characteristics of equine endometrial fibroblasts. Tissue fibrosis is described as the excessive accumulation of extracellular matrix (ECM) components. This process is associated with inflammation, and the interaction between fibroblasts and immune cells plays a key role, driving the progression of fibrosis. Results of recent study suggest that interleukin (IL)-12 may play a role in the processes associated with the development of fibrosis. This proinflammatory cytokine is synthesized and released by macrophages, dendritic cells, and B cells. Objective: The objective of this study was to determine: (i) the expression of IL-12 and its receptor ...
Combined PRP and CCP Therapy Suppresses Inflammation and Protects Cartilage in Post-Traumatic Osteoarthritis. This study aimed to evaluate the therapeutic effects of platelet-rich plasma (PRP) and Cervus and Cucumis polypeptide (CCP) injections in rats with post-traumatic osteoarthritis (OA). The model was established by transection of the anterior cruciate ligament, and the animals were subsequently treated with PRP and CCP. Articular cartilage degeneration was assessed through gross morphological observation, histopathological staining, and a standardized scoring system. Concurrently, pain-related behaviors, joint swelling, levels of inflammatory cytokines, and markers associated with extracellular ...
Proteomic signatures of equine dental tooth tissues in ageing and disease. Ageing and dental disease in horses lead to structural and functional deterioration of dental tissues, yet their molecular signatures remain poorly characterised. Understanding how these processes alter the protein composition of enamel, dentin, cementum and pulp is essential for improving equine oral health and identifying biomarkers of degeneration. Objective: To characterise the proteomic profiles of equine dental tissues and determine age- and disease-associated changes, with the aim of identifying proteins consistently altered across conditions. Methods: Ex vivo proteomic study. Methods: ...
Allogeneic Platelet-Rich Gel Supernatant Reprograms the Cytokine and Growth Factor Microenvironment in an Equine In Vitro Inflammatory Tendon System. Tendinopathy involves a dysregulated inflammatory microenvironment in which cytokines, growth factors (GF) and extracellular matrix components interact dynamically. Platelet-rich plasma (PRP) is widely used as a regenerative therapy, but its mechanisms of action in inflamed tendon remain unclear. This study evaluated whether platelet-rich gel supernatant (PRGS) reprograms the inflammatory-anabolic mediator network in an equine in vitro tendon explant system stimulated with lipopolysaccharide (LPS). Tendon explants were cultured under six experimental conditions, including non-stimulated contro...
Multiple strategies, one mission: mesenchymal stromal cell-based mechanisms of action in osteoarthritis. Osteoarthritis (OA) is a cross-species, multifactorial joint disease characterized by the progressive degeneration of articular cartilage, morphological remodeling of the subchondral bone, and inflammatory and fibrotic changes of the joint capsule. These alterations arise from chronic, often subclinical, inflammatory processes and dysregulated cellular homeostasis, leading to profound shifts in the cellular and extracellular composition of the joint organ. Although the mechanisms driving persistent inflammation are only partially understood, their impact on all joint-associated tissues is well...
Interleukins decrease epithelial protein and gene expression by K14 + CD105+ equine hoof progenitor cells. Background: Progenitor cell epithelial to mesenchymal transition (EMT) could impact healing in the epidermal-dermal junction of the equine hoof stratum internum (SI). The hypothesis of this study was that K14 + CD105+ equine hoof SI progenitor cells assume a mesenchymal phenotype in the presence of inflammatory interleukins in vitro.Methods: K14 + CD105+ progenitor cell percentages isolated from proliferative scarred (fibrous) and healthy SI were quantified. Decellularized matrix was prepared from and K14 + CD105+ cells localized in healthy SI. Gene expression (CD44, CD105, E-cadhe...
Cannabidiol-induced cellular and matrix-associated responses in primary equine sarcoid cells. Sarcoids are locally invasive skin tumors in equids, associated with bovine papillomavirus. Objective: Address potential applications of cannabidiol (CBD) in veterinary medicine. We evaluated the response of equine sarcoid cells to CBD in vitro, focusing on viability, invasiveness, and matrix remodeling. Methods: Three primary sarcoid cell lines. Methods: Cells were treated with CBD (20, 6.75, 2.25, 0.75 μM) and incubated for 6, 24, 48, 72 hours. Cell viability, cytotoxicity, and apoptosis were assessed using the ApoTox-Glo Assay. Based on these results, further analyses were performed for ...
Interleukin-4 changes the transcriptome, ECM-associated components and function of mare endometrial fibroblast: Insights from healthy and fibrotic cells. Fibrosis remains incompletely understood, particularly in terms of how immune mediators shape stromal programs. We used a spontaneous large‑animal model-endometrosis (equine endometrial fibrosis) to define how interleukin‑4 (IL‑4) reprograms fibroblasts from healthy and fibrotic endometrium. Primary fibroblasts were exposed to IL‑4 (10 ng/mL) for 48 or 96 h. At 48 h, bulk transcriptomes revealed 1307 differentially expressed genes (DEGs; 648 up, 659 down) and 1271 DEGs (645 up, 626 down) in fibroblasts derived from endometria without or with endometrosis, respectively. Enrichment an...
TGF-β1 and estradiol modulate prostaglandin concentrations and related gene expression in equine endometrium during the follicular phase. Transforming growth factor (TGF)-β1 is a pro-fibrotic cytokine that affects extracellular matrix (ECM) deposition and fibroblast activity. 17β-Estradiol (E), the dominant ovarian steroid during the follicular phase (FLP) of the estrous cycle, can also influence ECM remodeling and fibrosis, through prostaglandin (PG) synthesis. PGs have opposing roles in fibrosis, with PGE₂ showing anti-fibrotic effects and PGF₂α promoting fibrosis. Equine endometrosis, whose main pathological feature is fibrosis, is marked by chronic inflammation and ECM accumulation, and may involve mediators like TGF-...
Engineered biopolymeric hydrogels for in vitro modeling of equine sarcoid tumors in comparative oncology. Developing advanced preclinical in vitro cancer models is essential for understanding tumor biology, improving drug discovery, and enhancing the clinical translation of new therapies. Papillomaviruses (PVs) cause diverse lesions in humans and animals; notably, bovine papillomavirus (BPV) is the main cause of equine sarcoid, the most common skin tumor in horses. Its pathogenesis involves viral infection, fibroblast transformation, and extracellular matrix (ECM) remodeling. These processes highlight the limitations of conventional two-dimensional (2D) culture systems, which fail to replicate the...
Single-cell atlas of the equine placenta reveals cellular heterogeneity and gestational-stage-associated programs. The placenta mediates critical interactions between mother and offspring that guide development and impact long-term health. Despite its importance, the cellular organization of the equine (Equus caballus) placenta remains poorly defined. The equine epitheliochorial placenta, characterized by the absence of trophoblast invasion and prominent endocrine activity, provides a unique comparative model for studying placental cellular composition and development. Methods: We applied single-cell RNA sequencing to chorioallantois tissue collected from first-trimester (n = 1) and term (n = 2) equine...
Comparative Analysis of Extracellular Vesicle Isolation From Equine Serum and Plasma Using Two Isolation Methods With Structural and Proteomic Validation. Extracellular vesicles (EVs) are promising biomarkers and mediators of intercellular communication, but their isolation from equine biofluids remains challenging. This study compared two isolation workflows-size-exclusion chromatography (SEC) and differential ultracentrifugation followed by SEC (UC + SEC)-to evaluate their efficiency, reproducibility, and the proteomic composition of EVs derived from equine serum and plasma. Blood from six healthy horses was processed to obtain platelet-free plasma and serum. EVs were isolated using SEC or UC + SEC and characterized by transmission ele...
The Effect of Training on the Expression of Protein and Metabolites in the Plasma Exosomes of the Yili Horse. The effects of physical exercise on protein expression and metabolites in the plasma exosomes of horses are not yet clear. This study aims to elucidate the effects of exercise training on the expression of plasma extracellular vesicle proteins and metabolites in horses through multi-omics analysis, providing reference indicators for the training and performance evaluation of horses. Methods: Eight healthy 3-year-old horses were selected for the study, with four untrained horses as the control group and four trained horses as the training group. After conducting proteomic and metabolomic an...
Exosome and miRNA Content Engagement in the Physical Exercise Response: What Is Known to Date in Atheltic Horses? To date, there is extensive scientific evidence affirming that physical exercise plays a fundamental role in both the prevention and treatment of various pathological conditions in humans as well as in animals. It is understood that the advantages of movement and exercise have a multifactorial origin and they depend on a category of bioactive molecules vehicolated by extracellular microvesicles known as exosomes. The exosomes act as potential delivery systems for messages within the organism. These findings have drawn significant attention, leading researchers to further investigate the role o...
Age-induced gene expression in Thoroughbred horse skeletal muscle highlights genes that enhance muscle architecture and function. Early skeletal muscle development is critical for young racehorses, yet research on the transcriptional changes during this period is limited. Additionally, the impact of age on the transcriptional response to exercise training in equine athletes is not well understood. A transcriptome-wide analysis of differential gene expression in skeletal muscle was performed for five untrained Thoroughbred horses sampled at rest at two years old (UR2) and three years old (UR3). A total of 136 differentially expressed genes (DEGs) were identified, with 95 increased and 41 decreased in expression. GO enrich...
Transcriptomic Insights into Tumor Necrosis Factor α’s Role in the Fibrosis-Related Processes of Equine Endometrial Fibroblasts. Equine endometrosis is a chronic degenerative condition of the endometrium. A hallmark feature of endometrosis is endometrial fibrosis accompanied by degenerative changes in the adjacent tissue structure. Tumor necrosis factor α (TNFα), a pleiotropic cytokine produced by various immune cells, plays a dual role in coordinating immune responses and regulating cell/tissue homeostasis, making it an important regulator of fibrotic-related disorders. However, the exact role of TNFα in the development of equine endometrial fibrosis remains to be discovered and explained. Therefore, the main aim of...
Collagen composition in equine exuberant granulation tissue reflects tissue immaturity. Exuberant granulation tissue (EGT) is a second intention wound healing disorder. It commonly occurs in the distal limb of horses. EGT causes significant increase in the duration and cost of treatment, potentially leading to the decision not to pursue treatment and euthanize the patient. The underlying pathomechanisms of this fibroproliferative disorder remain unclear, particularly in terms of collagen composition and the association between myofibroblasts and blood vessels. This study investigated the collagen composition in naturally occurring EGT following trimming in 19 horses (EGT group). ...
Cellular interactions and gene expression analysis of two equine-derived bone graft materials: an in vitro study. Bone grafting is a surgical procedure that involves the use of bone tissue or bone substitutes to repair damaged bone. In dentistry and maxillofacial surgery, bone graft substitutes from various sources are commonly used. Given their critical role in clinical outcomes, it is essential to thoroughly investigate the biological and mechanical properties of these materials. Methods: In this in vitro study, we evaluated the biological properties of two equine-derived bone graft substitutes in comparison to β-tricalcium phosphate. The materials included one equine-derived graft containing hydrolyze...
Equine adipose-derived stem cells modulate in vitro neutrophil extracellular trap release by polymorphonuclear neutrophils. Neutrophil extracellular trap (NET) are thin and long web-like structures composed of DNA and antimicrobial proteins released by activated polymorphonuclear neutrophils (PMN) as part of the innate immune response. Adipose-derived stem cells (ADSCs) represent an accessible, abundant and minimal invasive source of mesenchymal stem cells (MSCs), with high regenerative potential, immunomodulatory and anti-inflammatory properties. Although recognized immunomodulatory properties of ADSCs, their interaction with PMN and their role on NET formation remains poorly characterized. The present study aimed...
Th1 and Th2 cells in equine endometrosis and their interactions with endometrial fibroblasts. Mare endometrosis is a chronic degenerative condition of the endometrium, primarily characterized by fibrosis, involving interactions among fibroblasts, immune cells, and epithelial cells regulated by cytokines and growth factors. T helper (Th)1 and Th2 cells seem to play a pivotal role in fibrosis. However, their roles in equine endometrial fibrosis remain unknown. This study explores Th1 and Th2 cell distribution across different stages of endometrium histopathological Kenney and Doig categories; and evaluated their secretome effects on non-fibrotic endometrium derived fibroblast functional ...
Proteoglycan 4 is expressed in equine flexor tendons and tendon sheaths, with greater synovial fluid lubricin in tendon sheaths with tendon injury. To describe proteoglycan 4 (PRG4) expression, lubricin tissue distribution, and lubricin synovial fluid concentrations in healthy and injured equine flexor tendons and tenosynovial structures. Unassigned: Synovial fluid and tissues were collected over the span of 1 year. Proteoglycan 4 expression was quantified using quantitative real-time PCR, lubricin synovial fluid concentrations were measured using ELISAs, and lubricin tissue distribution was evaluated with immunohistochemistry. Histology and quantitative real-time PCR data for healthy samples were analyzed using paired t tests, repeated-m...
Proteomic profiling of endometrial tissue and plasma from mares with endometrial fibrosis†. Endometrial fibrosis leads to subfertility when periglandular fibrosis impairs endometrial gland function. Identifying distinct protein expressions in mares suffering from this condition is essential for understanding the pathogenesis and developing treatments to delay fibrotic progression. To gain a better understanding of protein dynamics underlying this condition, Data-Independent Acquisition Mass Spectrometry was utilized to comprehensively characterize and compare the equine endometrial and plasma proteome from mares with different severities of endometrial fibrosis. Mares in diestrus wer...
Interleukin 17A in the fibrotic-related processes in endometrosis in the mare. Equine endometrosis is a chronic degenerative condition with fibrosis being one of the most significant characteristics. A growing body of evidence indicates the critical role of interleukin (IL)-17 in fibrotic disorders. However, its exact role during equine endometrosis remains to be discovered and explained. The main aim of the current study was to establish the expression of IL-17A signaling components in equine endometria with and without endometrosis as well as the effects of IL-17A on the transcriptomic signature, cellular functional characteristics, expression of extracellular matrix (...
Extracellular Vesicles Derived From Endometrial Stem Cells Preconditioned With PGE2-Reverse Myofibroblast Phenotype in Mare Endometrial Cells: A Novel Anti-Fibrotic Approach. Endometrial fibrosis in mares compromises fertility through aberrant extracellular matrix deposition and sustained myofibroblast activation. Conventional interventions fail to reverse these pathological alterations, necessitating innovative, mechanism-focused therapies. In this study, we pioneered the use of prostaglandin E2 (PGE2) preconditioning of equine endometrial-derived mesenchymal stem cells (ET-eMSCs) and their extracellular vesicles (EVs) to target fibrotic processes directly. ET-eMSCs were isolated from mare endometrial biopsies pretreated with PGE2 to enhance their anti-fibrotic se...
Comparative Transcriptome and MicroRNA Profiles of Equine Mesenchymal Stem Cells, Fibroblasts, and Their Extracellular Vesicles. Mesenchymal stem cells (MSCs) are a promising tool in regenerative medicine due to their ability to secrete paracrine factors that modulate tissue repair. Extracellular vesicles (EVs) released by MSCs contain bioactive molecules (e.g., mRNAs, miRNAs, proteins) and play a key role in intercellular communication. This study compared the transcriptomic profiles (mRNA and miRNA) of equine MSCs derived from adipose tissue (AT-MSCs), bone marrow (BM-MSCs), and ovarian fibroblasts (as a differentiated control). Additionally, miRNAs present in EVs secreted by these cells were characterized using nex...
RNA Sequencing on Muscle Biopsies from Exertional Rhabdomyolysis Patients Revealed Down-Regulation of Mitochondrial Function and Enhancement of Extracellular Matrix Composition. Exertional rhabdomyolysis (ER) is primarily driven by mechanical stress on muscles during strenuous or unaccustomed exercise, often exacerbated by environmental factors like heat and dehydration. While the general cellular pathway involving energy depletion and calcium overload is understood in horse ER models, the underlying mechanisms specific to the ER are not universally known within humans. This study aimed to evaluate whether patients with ER exhibited transcriptional signatures that were significantly different from those of healthy individuals. Methods: This study utilized RNA sequenci...
Tendon/Ligaments: Structure and Composition. The mid-metacarpal SDFT, intrasynovial DDFT and suspensory ligament are frequently injured soft tissues in the equine athlete. The mid-metacarpal SDFT exhibits a hierarchical structure and encounters repetitive strains at its functional limit. The intrasynovial DDFT possesses fibrocartilage where opposing bony surfaces to facilitate resistance-free gliding and contains chondrocyte-like cells embedded in a proteoglycan-rich ECM. While suspensory ligament enthesis injuries are common, collagen and non-collagen ECM structure-function specializations at the bone-ligament interface are understudied...
Quantitative proteomics unveils potential plasma biomarkers and provides insights into the pathophysiological mechanisms underlying equine metabolic syndrome. Equine Metabolic Syndrome (EMS) is a multifactorial endocrine disorder characterized by obesity, insulin dysregulation (ID), and an increase in the risk of laminitis, a painful condition that can lead to euthanasia in severe cases. Diagnosing EMS is challenging and often relies on clinical history including obesity, difficulty in losing weight, and recurring episodes of laminitis. The gold standard for laboratory support of an EMS diagnosis is the identification of ID, with basal insulin being the simplest and most accessible method, especially in a field setting. However, various factors such...
