Topic:Cartilage
Cartilage in horses is a specialized connective tissue found in joints, providing a smooth, lubricated surface for articulation and facilitating the transmission of loads with low friction. It is composed of chondrocytes embedded within an extracellular matrix rich in collagen fibers, proteoglycans, and water. Cartilage does not contain blood vessels or nerves, relying on diffusion for nutrient delivery and waste removal. This avascularity contributes to its limited capacity for repair and regeneration. Research on equine cartilage focuses on understanding its structure, function, and the biological processes involved in cartilage development, maintenance, and degeneration. Studies also explore the impact of various conditions, such as osteoarthritis, on cartilage integrity and investigate potential therapeutic approaches for cartilage repair and preservation. This page gathers peer-reviewed research and scholarly articles that delve into the biology, pathology, and treatment of cartilage-related conditions in horses.
Lentiviral vector expression of Klf4 enhances chondrogenesis and reduces hypertrophy in equine chondrocytes. Monolayer expansion of chondrocytes in culture results in the dedifferentiation of chondrocytes with inferior cartilage specific extracellular matrix synthesis and proliferation when compared with its native counterpart. We aimed to enhance chondrocyte proliferation and articular cartilage specific gene expression through ectopic expression of the major pluripotency transcription factors (Oct4, Sox2, Klf4 and c-Myc). We also aimed to provide insights to the modulation of TGFβ receptor mRNA with Klf4 overexpression. Equine chondrocytes pooled from three donors were transduced with lentiviral v...
Effect of culture duration on chondrogenic preconditioning of equine bone marrow mesenchymal stem cells in self-assembling peptide hydrogel. Ex vivo induction of chondrogenesis is a promising approach to improve upon the use of bone marrow mesenchymal stem cells (MSCs) for cartilage tissue engineering. This study evaluated the potential to induce chondrogenesis with days of culture in chondrogenic medium for MSCs encapsulated in self-assembling peptide hydrogel. To simulate the transition from preconditioning culture to implantation, MSCs were isolated from self-assembling peptide hydrogel into an individual cell suspension. Commitment to chondrogenesis was evaluated by seeding preconditioned MSCs into agarose and culturing in the ...
Aging does not change the compressive stiffness of mandibular condylar cartilage in horses. Aging can cause an increase in the stiffness of hyaline cartilage as a consequence of increased protein crosslinks. By induction of crosslinking, a reduction in the diffusion of solutions into the hyaline cartilage has been observed. However, there is a lack of knowledge about the effects of aging on the biophysical and biochemical properties of the temporomandibular joint (TMJ) cartilage. Hence, the aim of this study was to examine the biophysical properties (thickness, stiffness, and diffusion) of the TMJ condylar cartilage of horses of different ages and their correlation with biochemical p...
Assessment of effectiveness and safety of repeat administration of proinflammatory primed allogeneic mesenchymal stem cells in an equine model of chemically induced osteoarthritis. This study aimed at assessing the effectiveness and safety of repeated administrations of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) primed with tumor necrosis factor (TNF)-α and interferon-γ in an equine model of chemically-induced osteoarthritis. Arthritis was induced in both radio-carpal (RC)-joints by amphotericin-B in 18 ponies, divided into three groups depending on the treatment injected: MSC-naïve (n = 7), MSC-primed (n = 7) and control (n = 4). The study consisted of two phases and used one RC-joint of each animal in each phase, with four months tim...
Functional anatomy of the equine temporomandibular joint: Histological characteristics of the articular surfaces and underlining tissues. It has been assumed that dental conditions cause disorders of the equine temporomandibular joint (TMJ), due to biomechanical overload or aberrant loading. However, the incidence of published TMJ disorders in horses is low and this leads to the question whether the equine TMJ is adapted well to its biomechanical requirements or is able to remodel its articular surfaces in response to modified loading conditions. The aim of this study was to determine the histological characteristics of healthy equine TMJs. The tissue components of the articular surfaces of 10 TMJs obtained from horses without a...
TGF-β1 upregulates the expression of hyaluronan synthase 2 and hyaluronan synthesis in culture models of equine articular chondrocytes. We investigated the effect of transforming growth factor beta 1 (TGF-β1) on equine hyaluronan synthase 2 () gene expression and hyaluronan (HA) synthesis in culture models of articular chondrocytes. Equine chondrocytes were treated with TGF-β1 at different concentrations and times in monolayer cultures. In three-dimensional cultures, chondrocyte-seeded gelatin scaffolds were cultured in chondrogenic media containing 10 ng/mL of TGF-β1. The amounts of HA in conditioned media and in scaffolds were determined by enzyme-linked immunosorbent assays. mRNA expression was analyzed by semi-quantita...
Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation. Polyelectrolyte nanoparticle constructs (NPs) comprising salmon calcitonin (sCT), chitosan (CS), and hyaluronic acid (HA) were previously established as having anti-inflammatory potential when injected via the intra-articular (i.a.) route to a mouse model. We attempted to translate the formulation to a large animal model, the lipopolysaccharide (LPS)-stimulated equine model of joint inflammation. The aim was to manufacture under aseptic conditions to produce sterile pyrogen-free NPs, to confirm physicochemical characteristics, and to test toxicity and efficacy in a pilot study. NP dispersions ...
Expression of pro-apoptotic markers is increased along the osteochondral junction in naturally occurring osteochondrosis. Osteochondrosis (OC) is a naturally occurring disease of the articular-epiphyseal cartilage and subchondral bone layers, leading to pain and decreased mobility. The objective of this study was to characterize gene and protein expression of apoptotic markers in chondrocytes surrounding cartilage canals and along the osteochondral junction of osteochondrosis (OC)-affected and normal cartilage, using naturally occurring disease in horses. Paraffin-embedded osteochondral samples (6 OC, 8 normal controls) and cDNA from chondrocytes captured with laser capture microdissection (4 OC, 6 normal control...
Xenogenic Implantation of Equine Synovial Fluid-Derived Mesenchymal Stem Cells Leads to Articular Cartilage Regeneration. Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from t...
Septic Arthritis/Osteomyelitis May Lead to Osteochondrosis-Like Lesions in Foals. Failure of the cartilage canal blood supply leads to ischemic chondronecrosis which causes osteochondrosis, and osteochondral lesions. Osteochondrosis is a disease with a heritable component and usually occurs under aseptic conditions. Because bacteria can bind to growth cartilage and disrupt the blood supply in pigs and chickens, we considered whether this might play a role in development of equine osteochondrosis. The aim of this study was to examine whether bacteria are present in canals in the growth cartilage of foals with septic arthritis/osteomyelitis, and whether this is associated wit...
Biochemical and biomechanical characterisation of equine cervical facet joint cartilage. The equine cervical facet joint is a site of significant pathology. Located bilaterally on the dorsal spine, these diarthrodial joints work in conjunction with the intervertebral disc to facilitate appropriate spinal motion. Despite the high prevalence of pathology in this joint, the facet joint is understudied and thus lacking in viable treatment options. Objective: The goal of this study was to characterise equine facet joint cartilage and provide a comprehensive database describing the morphological, histological, biochemical and biomechanical properties of this tissue. Methods: Descriptive...
AAV-mediated Overexpression of IL-10 Mitigates the Inflammatory Cascade in Stimulated Equine Chondrocyte Pellets. Following joint trauma, a posttraumatic inflammatory cascade drives degeneration of the joint. We aimed to assess whether transduction of chondrocytes with AAV5 overexpressing the immunomodulatory cytokine IL-10 would have protective effects in pellet cultures stimulated with IL-1β. Chondrocytes were isolated from 3 healthy horses and were transduced with AAV5-IL-10 at a dose of 1 x 105vg/cell. Chondrocyte pellets were formed by centrifugation and were stimulated with IL-1β starting 48 hours following transduction. After 2, 6 and 14 days in culture, supernatants were collected for cytokine a...
Large Animal Models for Osteochondral Regeneration. Namely, in the last two decades, large animal models - small ruminants (sheep and goats), pigs, dogs and horses - have been used to study the physiopathology and to develop new therapeutic procedures to treat human clinical osteoarthritis. For that purpose, cartilage and/or osteochondral defects are generally performed in the stifle joint of selected large animal models at the condylar and trochlear femoral areas where spontaneous regeneration should be excluded. Experimental animal care and protection legislation and guideline documents of the US Food and Drug Administration, the American S...
Elevated Glucose Levels Preserve Glucose Uptake, Hyaluronan Production, and Low Glutamate Release Following Interleukin-1β Stimulation of Differentiated Chondrocytes. Chondrocytes are responsible for remodeling and maintaining the structural and functional integrity of the cartilage extracellular matrix. Because of the absence of a vascular supply, chondrocytes survive in a relatively hypoxic environment and thus have limited regenerative capacity during conditions of cellular stress associated with inflammation and matrix degradation, such as osteoarthritis (OA). Glucose is essential to sustain chondrocyte metabolism and is a precursor for key matrix components. In this study, we investigated the importance of glucose as a fuel source for matrix repair dur...
Critical-sized cartilage defects in the equine carpus. The horse joint, due to its similarity with the human joint, is the ultimate model for translational articular cartilage repair studies. This study was designed to determine the critical size of cartilage defects in the equine carpus and serve as a benchmark for the evaluation of new cartilage treatment options. Circular full-thickness cartilage defects with a diameter of 2, 4, and 8 mm were created in the left middle carpal joint and similar osteochondral (3.5 mm in depth) defects in the right middle carpal joint of 5 horses. Spontaneously formed repair tissue was examined macroscopically, ...
Culture of mesenchymal stem cells derived from equine synovial membrane in alginate hydrogel microcapsules. Mesenchymal stem cells derived from the synovial membrane (MSCSM) have a greater potential for joint regeneration, besides the capacity for chondrogenic differentiation, since they are a source closer to the chondrocytes. This study aimed to cultivate and evaluate viability and differentiation of MSC encapsulated in a three-dimensional alginate hydrogel (HA) scaffold. Samples of the synovial membrane of the metatarsophalangeal joint of 4 horses were collected by astroscopic surgery. These were subjected to enzymatic digestion, isolated mesenchymal cells, cultured in monolayers and encapsulated...
Effects of stanozolol on normal and IL-1β-stimulated equine chondrocytes in vitro. Intra-articular administration of stanozolol has shown promising results by improving the clinical management of lameness associated with naturally-occurring osteoarthritis (OA) in horses, and by decreasing osteophyte formation and subchondral bone reaction in sheep following surgically induced OA. However, there is limited evidence on the anti-inflammatory and modulatory properties of stanozolol on articular tissues. The objective of the current study was to evaluate the effects of stanozolol on chondrocyte viability and gene expression in normal equine chondrocytes and an inflammatory in vit...
Concepts and challenges in the use of mesenchymal stem cells as a treatment for cartilage damage in the horse. Osteoarthritis (OA), the most common form of joint disease affecting humans and horses, is characterized by the advance and decline of cartilage and loss of function of the affected joint. The progression of OA is steadily accompanied with biochemical events, which interfere with the cytokines and proteolytic enzymes responsible for progress of the disease. Recently, regenerative therapies have been used with an assumption that mesenchymal stem cells (MSCs) possess the potential to prevent the advancement of cartilage damage and potentially regenerate the injured tissue with an ultimate goal o...
Structure-Function relationships of equine menisci. Meniscal pathologies are among the most common injuries of the femorotibial joint in both human and equine patients. Pathological forces and ensuing injuries of the cranial horn of the equine medial meniscus are considered analogous to those observed in the human posterior medial horn. Biomechanical properties of human menisci are site- and depth- specific. However, the influence of equine meniscus topography and composition on its biomechanical properties is yet unknown. A better understanding of equine meniscus composition and biomechanics could advance not only veterinary therapies for meni...
The ghrelin paradox in the control of equine chondrocyte function: The good and the bad. Increasing evidence suggests a role for ghrelin in the control of articular inflammatory diseases like osteoarthritis (OA). In the present study we examined the ability of ghrelin to counteract LPS-induced necrosis and apoptosis of chondrocytes and the involvement of GH secretagogue receptor (GHS-R)1a in the protective action of ghrelin. The effects of ghrelin (10-10 mol/L) on equine primary cultured chondrocytes viability and necrosis in basal conditions and under LPS treatment (100 ng/ml) were detected by using both acridine orange/propidium iodide staining and annexin-5/propidium iodide...
Progenitor cells in auricular cartilage demonstrate cartilage-forming capacity in 3D hydrogel culture. Paramount for the generation of auricular structures of clinically-relevant size is the acquisition of a large number of cells maintaining an elastic cartilage phenotype, which is the key in producing a tissue capable of withstanding forces subjected to the auricle. Current regenerative medicine strategies utilize chondrocytes from various locations or mesenchymal stromal cells (MSCs). However, the quality of neo-tissues resulting from these cell types is inadequate due to inefficient chondrogenic differentiation and endochondral ossification, respectively. Recently, a subpopulation of stem/pr...
Use of a 3-Telsa magnet to perform delayed gadolinium-enhanced magnetic resonance imaging of the distal interphalangeal joint of horses with and without naturally occurring osteoarthritis. OBJECTIVE To characterize delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) features of healthy hyaline cartilage of the distal interphalangeal joint (DIPJ) of horses, to determine whether dGEMRIC can be used to differentiate various stages of naturally occurring osteoarthritis of the DIPJ, and to correlate relaxation times determined by dGEMRIC with the glycosaminoglycan concentration, water content, and macroscopic and histologic findings of hyaline cartilage of DIPJs with and without osteoarthritis. SAMPLE 1 cadaveric forelimb DIPJ from each of 12 adult warmblood horses. PROCEDURES T1-...
Comparison between magnetic resonance imaging, computed tomography, and arthrography to identify artificially induced cartilage defects of the equine carpal joints. While articular cartilage changes are considered to be one of the initial events in the pathological cascade leading to osteoarthritis, these changes remain difficult to detect using conventional diagnostic imaging modalities such as plain radiography. The aim of this prospective, experimental, methods comparison study was to compare the sensitivity of magnetic resonance imaging (MRI), magnetic resonance arthrography, computed tomography (CT), and CT arthrography in the detection of artificially induced articular cartilage defects in the equine carpal joints. Defects were created in the antebr...
Chondrogenic Differentiation of Defined Equine Mesenchymal Stem Cells Derived from Umbilical Cord Blood for Use in Cartilage Repair Therapy. Cartilage engineering is a new strategy for the treatment of cartilage damage due to osteoarthritis or trauma in humans. Racehorses are exposed to the same type of cartilage damage and the anatomical, cellular, and biochemical properties of their cartilage are comparable to those of human cartilage, making the horse an excellent model for the development of cartilage engineering. Human mesenchymal stem cells (MSCs) differentiated into chondrocytes with chondrogenic factors in a biomaterial appears to be a promising therapeutic approach for direct implantation and cartilage repair. Here, we cha...
Improvement of the Chondrocyte-Specific Phenotype upon Equine Bone Marrow Mesenchymal Stem Cell Differentiation: Influence of Culture Time, Transforming Growth Factors and Type I Collagen siRNAs on the Differentiation Index. Articular cartilage is a tissue characterized by its poor intrinsic capacity for self-repair. This tissue is frequently altered upon trauma or in osteoarthritis (OA), a degenerative disease that is currently incurable. Similar musculoskeletal disorders also affect horses and OA incurs considerable economic loss for the equine sector. In the view to develop new therapies for humans and horses, significant progress in tissue engineering has led to the emergence of new generations of cartilage therapy. Matrix-associated autologous chondrocyte implantation is an advanced 3D cell-based therapy that...
Evaluation of conjugated linoleic acid supplementation on markers of joint inflammation and cartilage metabolism in young horses challenged with lipopolysaccharide. Seventeen yearling Quarter Horses were used in a randomized complete block design for a 56-d trial to determine ability of dietary CLA to mitigate joint inflammation and alter cartilage turnover following an inflammatory insult. Horses were blocked by age, sex, and BW, and randomly assigned to dietary treatments consisting of commercial concentrate offered at 1% BW (as-fed) supplemented with either 1% soybean oil (CON; n = 6), 0.5% soybean oil and 0.5% CLA (LOW; n = 5; 55% purity; Lutalin, BASF Corp., Florham Park, NJ), or 1% CLA (HIGH; n = 6) top-dressed daily. Horses were fed individually ev...
Detecting selection signatures on the X chromosome of the Chinese Debao pony. The X chromosome shows a special interaction between demographic factors and genetic variation, and the analysis of X-linked genomic variation can therefore provide insights into the unique effects of demography and selection on the horse genome that cannot be readily detected by autosomal markers. Debao (DB) ponies have experienced intense selective pressure for the development of their small stature (<106 cm at adult height). To identify selective sweeps on the X chromosome of the DB pony, we performed a genome-wide scan of three Chinese horse breeds using an Equine SNP70 BeadChip. Using Yi...
Minimally Manipulated Bone Marrow Concentrate Compared with Microfracture Treatment of Full-Thickness Chondral Defects: A One-Year Study in an Equine Model. Microfracture is commonly performed for cartilage repair but usually results in fibrocartilage. Microfracture augmented by autologous bone marrow concentrate (BMC) was previously shown to yield structurally superior cartilage repairs in an equine model compared with microfracture alone. The current study was performed to test the hypothesis that autologous BMC without concomitant microfracture improves cartilage repair compared with microfracture alone. Methods: Autologous sternal bone marrow aspirate (BMA) was concentrated using a commercial system. Cells from BMC were evaluated for chondroge...
Evaluation of equine synovial-derived extracellular matrix scaffolds seeded with equine synovial-derived mesenchymal stem cells. OBJECTIVE To create a bioactive synovium scaffold by infusing decellularized synovial-derived extracellular matrix (synECM) with synovial-derived mesenchymal stem cells (synMSCs). SAMPLE Synovium from the femoropatellar and medial femorotibial joints of equine cadavers. PROCEDURES The synMSCs were cultured in monolayer and not treated or cotransduced to enhance expression of green fluorescent protein (GFP) and human bone morphogenetic protein (BMP)-2. The synECM was decellularized with 0.1% peracetic acid and then seeded with synMSCs (0.5 × 10 cells/0.5 mL) by use of a 30% serum gradient. Sam...
Effect of intra-articular administration of superparamagnetic iron oxide nanoparticles (SPIONs) for MRI assessment of the cartilage barrier in a large animal model. Early diagnosis of cartilage disease at a time when changes are limited to depletion of extracellular matrix components represents an important diagnostic target to reduce patient morbidity. This report is to present proof of concept for nanoparticle dependent cartilage barrier imaging in a large animal model including the use of clinical magnetic resonance imaging (MRI). Conditioned (following matrix depletion) and unconditioned porcine metacarpophalangeal cartilage was evaluated on the basis of fluorophore conjugated 30 nm and 80 nm spherical gold nanoparticle permeation and multiphoton lase...