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.
Gene Delivery to Chondrocytes. Delivering genes to chondrocytes offers new possibilities both clinically, for treating conditions that affect cartilage, and in the laboratory, for studying the biology of chondrocytes. Advances in gene therapy have created a number of different viral and non-viral vectors for this purpose. These vectors may be deployed in an ex vivo fashion, where chondrocytes are genetically modified outside the body, or by in vivo delivery where the vector is introduced directly into the body; in the case of articular and meniscal cartilage in vivo delivery is typically by intra-articular injection. Ex viv...
Interleukin-1β and methylprednisolone acetate demonstrate differential effects on equine deep digital flexor tendon and navicular bone fibrocartilage cells in vitro. To investigate the effects of interleukin-1β (IL-1β) and methylprednisolone acetate (MPA) on equine intrabursal deep digital flexor tendon (DDFT) and navicular bone fibrocartilage (NBF) cells in vitro. Methods: Third passage DDFT and NBF cells from 5 healthy donor horses ages 11-17 years euthanized for reasons unrelated to musculoskeletal conditions. Methods: Aggregate cultures were incubated with culture medium alone (control), 10 ng/mL IL-1β, 10 ng/mL IL-1β + 0.05 mg/mL MPA, or 10 ng/mL IL-1β + 0.5 mg/mL MPA for 24 hours. Extracellular matrix (ECM) gene expressions were assessed via rea...
Evaluation of cartilage injury in horses with osteochondral fragments in the metacarpo-/metatarsophalangeal joint: A study on 823 arthroscopies. Osteochondral fragment removal is commonly performed but there are little scientific data supporting this procedure in the absence of clinical signs. More information is needed to facilitate clinical decision-making regarding fragment removal of the metacarpo-/metatarsophalangeal joint. Objective: To assess prevalence of cartilage injury in the equine metacarpo-/metatarsophalangeal joint and its association to fragment size, location, age and lameness. Methods: Retrospective observational study. Methods: Clinical records, including radiographs of 823 metacarpo-/metatarsophalangeal joints (640 ...
Correlation of Arthroscopic Grading and Optical Coherence Tomography as Markers of Early Repair and Predictors of Later Healing Evident on MRI and Histomorphometric Assessment of Cartilage Defects Implanted with Chondrocytes Overexpressing IGF-I. Injury of articular cartilage is common, and due to the poor intrinsic capabilities of chondrocytes, it can precipitate joint degradation and osteoarthritis (OA). Implantation of autologous chondrocytes into cartilaginous defects has been used to bolster repair. Accurate assessment of the quality of repair tissue remains challenging. This study aimed to investigate the utility of noninvasive imaging modalities, including arthroscopic grading and optical coherence tomography (OCT) for assessment of early cartilage repair (8 weeks), and MRI to determine long-term healing (8 months). Large (15 mm...
Equine osteoarthritis: Strategies to enhance mesenchymal stromal cell-based acellular therapies. Osteoarthritis (OA) is a degenerative disease that eventually leads to the complete degradation of articular cartilage. Articular cartilage has limited intrinsic capacity for self-repair and, to date, there is no curative treatment for OA. Humans and horses have a similar articular cartilage and OA etiology. Thus, in the context of a One Health approach, progress in the treatment of equine OA can help improve horse health and can also constitute preclinical studies for human medicine. Furthermore, equine OA affects horse welfare and leads to significant financial losses in the equine industry....
A one-health perspective: use of hemoderivative regenerative therapies in canine and equine patients. Regenerative medicine therapies have become significant tools for treatment of joint, soft tissue, and a variety of other conditions in animals and humans. Regenerative medicine aims to restore form and function of injured tissues using the body's own resources such as cells, fluids (ie, plasma and serum), and their resulting anti-inflammatory and prohealing cytokines. Platelet-rich plasma and other hemoderivatives have application for joint disorders such as osteoarthritis, cartilage injury, synovitis, and soft tissue injuries. These therapies achieve anti-inflammatory and healing effects wit...
New trends for osteoarthritis: Biomaterials, models and modeling. The burden of osteoarthritis (OA), one of the major causes of functional disabilities in humans and animals, continues to increase worldwide while no disease-modifying OA drugs (DMOADs) that either slow down or reverse disease progression have been made available. Here, we provide a brief overview of recent advances in: designing new OA drug delivery approaches, focusing on lubrication-based biomaterials and drug delivery systems, such as hydrogels, liposomes, dendrimers, micro- and nanoparticles; using either large (horse) or small (zebrafish) relevant animal models to evaluate new therapeuti...
Role of cartilage and bone matrix regulation in early equine osteochondrosis. The objective of this study is to better understand the pathogenesis of early equine osteochondrosis (OC) by identifying differences in gene and protein expression of extracellular matrix components and regulators in normal and diseased cartilage and bone, focusing on the osteochondral junction and cells surrounding the cartilage canals. We expected to find an upregulation of matrix metalloproteinases and a decrease in extracellular matrix constituent expression along the osteochondral junction and cells surrounding the cartilage canals in OC samples. Paraffin-embedded osteochondral samples (6...
Osteoarthritis animal models for biomaterial-assisted osteochondral regeneration. Clinical therapeutics for the regeneration of osteochondral defects (OCD) in the early stages of osteoarthritis remain an enormous challenge in orthopaedics. For in-depth studies of tissue engineering and regenerative medicine in terms of OCD treatment, the utility of an optimal OCD animal model is crucial for assessing the effects of implanted biomaterials on the repair of damaged osteochondral tissues. Currently, the most frequently used in vivo animal models for OCD regeneration include mice, rats, rabbits, dogs, pigs, goats, sheep, horses and nonhuman primates. However, there is no single ...
Preclinical Use of FGF-18 Augmentation for Improving Cartilage Healing Following Surgical Repair: A Systematic Review. To evaluate the efficacy of fibroblast growth factor-18 (FGF-18) augmentation for improving articular cartilage healing following surgical repair in preclinical () animal models. A systematic review was performed evaluating the efficacy of FGF-18 augmentation with cartilage surgery compared with cartilage surgery without FGF-18 augmentation in living animal models. Eligible intervention groups were FGF-18 treatment in conjunction with orthopedic procedures, including microfracture, osteochondral auto/allograft transplantation, and cellular-based repair. Outcome variables were: International Ca...
Concentrations of dexmedetomidine and effect on biomarkers of cartilage toxicity following intra-articular administration in horses. The goal of this study was to determine plasma, urine, and synovial fluid concentrations and describe the effects on biomarkers of cartilage toxicity following intra-articular dexmedetomidine administration to horses. Methods: 12 research horses. Methods: Horses received a single intra-articular administration of 1 μg/kg or 5 μg/kg dexmedetomidine or saline. Plasma, urine, and synovial fluid were collected prior to and up to 48 hours postadministration, and concentrations were determined. The effects on CS846 and C2C were determined in synovial fluid at 0, 12, and 24 hours postadministration...
T2 mapping of cartilage in the equine distal interphalangeal joint with corresponding histology using 0.27 T and 3.0 T magnetic resonance imaging. Low-field magnetic resonance imaging (MRI) is widely available to equine veterinarians yet is insensitive at detecting cartilage damage in the distal interphalangeal joint (DIPJ). T2 mapping is a quantitative imaging technique that can detect cartilage damage before morphological change is apparent. Objective: Validation of a T2 mapping sequence on a low-field MR system. Correlation of the mean T2 relaxation time in sections of cartilage with varying levels of pathology using low- and high-field MRI. Methods: Cross-sectional study. Methods: Eight phantoms with known (nominal) T2 values underwe...
Cartilage-Sparing Properties of Equine Omega Complete in an Organ Culture Model of Cartilage Inflammation. The purpose of this study was to determine anti-inflammatory and/or chondroprotective effects of Equine Omega Complete (EOC) on cartilage explants stimulated with lipopolysaccharide (LPS). Explants were aseptically prepared from the intercarpal joints of 17 market-weight pigs and placed in culture at 37°C for a total of 120 hours. For the final 96 hours, explants were conditioned with a simulated digestion extract of EOC (0, 36 or 180 μL/mL), and for the final 48 hours explants were stimulated with LPS (0 or 15µg/mL). Media was removed and replaced every 24 hours. Samples from the final 48 ...
Cartilaginous Intrusion of the Atrioventricular Node in a Quarter Horse with a High Burden of Second-Degree AV Block and Collapse: A Case Report. Second-degree atrioventricular (AV) block is the most common cardiac arrhythmia in horses, affecting 40-90% depending on breed. Usually, the AV blocks occur while the horses are resting and disappear upon exercise and are, therefore, considered to be uneventful for horses. However, if the AV blocks occur frequently, this may result in syncope and collapse. Identifying the cause of second-degree AV block is difficult and often subscribed to high vagal tone. In this report, we present an eight-year-old Quarter horse with a high burden of second-degree AV blocks and multiple collapses. The clinic...
Clodronate disodium is neither cytotoxic nor cytoprotective to normal and recombinant equine interleukin-1β-treated joint tissues in vitro. To determine the effects of clodronate disodium (CLO) on control and recombinant equine interleukin-1β (IL-1β)-treated equine joint tissues. Methods: In vitro experimental study. Methods: Cartilage explants, chondrocytes, and synoviocytes (n = 3 horses). Methods: Monolayer cultures of chondrocytes and synoviocytes from three horses were subjected to: control media (CON), 5 ng/ml CLO (C/low), 50 ng/ml CLO (C/med), 100 ng/ml CLO (C/high), with and without IL-1β, and 10 ng/ml IL-1β (IL) alone for 72 hours. Cartilage explants from three horses were subjected to CON, IL, C/low, and C/...
Optical photothermal infrared spectroscopy can differentiate equine osteoarthritic plasma extracellular vesicles from healthy controls. Equine osteoarthritis is a chronic degenerative disease of the articular joint, characterised by cartilage degradation resulting in pain and reduced mobility and thus is a prominent equine welfare concern. Diagnosis is usually at a late stage through clinical examination and radiographic imaging, whilst treatment is symptomatic not curative. Extracellular vesicles are nanoparticles that are involved in intercellular communication. The objective of this study was to investigate the feasibility of Raman and Optical Photothermal Infrared Spectroscopies to detect osteoarthritis using plasma-derive...
Differentiation of equine mesenchymal stem cells into cells of osteochondral lineage: potential for osteochondral tissue engineering. Damage to the hyaline cartilage of the joint surface and osteochondral fractures are key factors leading to the development of osteoarthritis in racehorses, representing a significant cause of racehorse retirement. To tissue-engineer an osteochondral unit that is suitable for joint repair, incorporation of a zone of calcified cartilage should be considered so as to mimic itscounterpart. To date, equine mesenchymal stem cells (eMSCs) have been reported to have multilineage differentiation potential. Yet the generation of a zone of calcified cartilage using eMSCs has not been reported. This work...
Synovium secretome as a disease-modifying treatment for equine osteoarthritis. To identify chondroprotective factors as potential disease-modifying osteoarthritis treatments using an unbiased, bottom-up proteomics approach. Methods: Paired equine cartilage explants and synovial membrane were collected postmortem from 4 horses with no history of lameness and grossly normal joints at necropsy. Methods: Six groups were established: cartilage, synoviocytes, and cartilage + synoviocytes (coculture), all with or without interleukin (IL)-1β. The catabolic effect of IL-1β was verified by glycosaminoglycan (GAG) released from cartilage into media by 1,9-dimethyl-methylene blue ...
Functionalized Nanogels with Endothelin-1 and Bradykinin Receptor Antagonist Peptides Decrease Inflammatory and Cartilage Degradation Markers of Osteoarthritis in a Horse Organoid Model of Cartilage. Osteoarthritis (OA) is a degenerative and heterogeneous disease that affects all types of joint structures. Current clinical treatments are only symptomatic and do not manage the degenerative process in animals or humans. One of the new orthobiological treatment strategies being developed to treat OA is the use of drug delivery systems (DDS) to release bioactive molecules over a long period of time directly into the joint to limit inflammation, control pain, and reduce cartilage degradation. Two vasoactive peptides, endothelin-1 and bradykinin, play important roles in OA pathogenesis. In this ...
Differential expression and methylation patterns of NFATC1, NADSYN1 and JAK3 gene in equine chondrocytes expanded in monolayer culture. Ex vivo expansion of chondrocytes in monolayer (ML) culture for therapeutic purposes is burdened with difficulties related to the loss of cartilaginous phenotype. Epigenetic mechanisms responsible for regulation of gene expression are believed to underlie chondrocyte dedifferentiation. We have inspected the relevance of DNA methylation alterations for passage-related differential expression of NFATC1 gene involved in hard connective tissue turnover and development, NADSYN1 influencing redox metabolism, and JAK3 - an important driver of inflammation. We have assessed relative amount of transcri...
A detailed macroscopic scoring system for experimental post-traumatic Osteoarthritis in the equine middle carpal joint. Osteoarthritis (OA) is a significant health issue in humans as well as horses. Experimental models of equine carpal OA have been used to investigate OA pathogenesis and potential therapeutic candidates. A 5-scale scoring system (OARSI) for macroscopic pathological cartilage changes already exists, but there is a need for a scoring system with better differentiation of severity. The aim of this study was therefore to develop and validate such a scoring system. Results: New scoring system were developed for cartilage erosions (Copenhagen Equine Total Cartilage Score, CEqTCS) along with synovial ...
Site- and Zone-Dependent Changes in Proteoglycan Content and Biomechanical Properties of Bluntly and Sharply Grooved Equine Articular Cartilage. In this study, we mapped and quantified changes of proteoglycan (PG) content and biomechanical properties in articular cartilage in which either blunt or sharp grooves had been made, both close to the groove and more remote of it, and at the opposing joint surface (kissing site) in equine carpal joints. In nine adult Shetland ponies, standardized blunt and sharp grooves were surgically made in the radiocarpal and middle carpal joints of a randomly chosen front limb. The contralateral control limb was sham-operated. At 39 weeks after surgery, ponies were euthanized. In 10 regions of interest (...
Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation. Allogenic mesenchymal stem cell (MSC) secretome is a novel intra-articular therapeutic that has shown promise in and small animal models and warrants further investigation. Unassigned: To investigate if intra-articular allogenic MSC-secretome has anti-inflammatory effects using an equine model of joint inflammation. Unassigned: Randomized positively and negatively controlled experimental study. Unassigned: In phase 1, joint inflammation was induced bilaterally in radiocarpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After 2 h, the secretome of INFy and TNFα stimul...
Detection of subtle cartilage and bone tissue degeneration in the equine joint using polarisation-sensitive optical coherence tomography. To explore the ability of polarisation-sensitive optical coherence tomography (PS-OCT) to rapidly identify subtle signs of tissue degeneration in the equine joint. Polarisation-sensitive optical coherence tomography (PS-OCT) images were systematically acquired in four locations along the medial and lateral condyles of the third metacarpal bone in five dissected equine specimens. Intensity and retardation PS-OCT images, and anomalies observed therein, were then compared and validated with high resolution images of the tissue sections obtained using Differential Interference contrast (DIC) optic...
Conditioned serum in vitro treatment of chondrocyte pellets and osteoarthritic explants. Autologous conditioned serum (ACS) is used to treat osteoarthritis in horses, although its effects are not fully investigated. Objective: To investigate the effects of equine serum and conditioned serum on chondrocytes stimulated with interleukin (IL)-1β and cartilage explants with mild osteoarthritis. Methods: In vitro experimental study. Methods: The effect of three different serum preparations (unincubated control [PS], serum incubated 24 h [PS24h] and serum incubated 24 h in ACS containers [PCS]) pooled from lame horses were tested in two in vitro models. IL-1β and IL-1 receptor anta...
Nerve growth factor receptors in equine synovial membranes vary with osteoarthritic disease severity. Nerve growth factor (NGF) is a neurotrophin that has been implicated in pain signaling, apoptosis, inflammation and proliferation. The resultant effects depend on interaction with two different receptors; tyrosine kinase A (TrkA) and p75 . NGF increases in synovial fluid from osteoarthritic joints, and monoclonal antibody therapy is trialed to treat osteoarthritis (OA)-related pain. Investigation of the complex and somewhat contradictory signaling pathways of NGF is conducted in neural research, but has not followed through to orthopaedic studies. The objectives of this study were to compare t...
The Impact of Circular Exercise Diameter on Bone and Joint Health of Juvenile Animals. Circular exercise is used in many equestrian disciplines and this study aimed to determine if circle diameter impacts juvenile animal forelimb bone and joint health. On day 0, 24 calves at 9 weeks of age were assigned the following exercise treatments: small circle (12 m clockwise), large circle (18-m clockwise), treadmill, or non-exercised control. Exercise was initiated at 1.1−1.5 m/s for 5 min/d and increased 5 min weekly until reaching 30 min/d. On day 49, synovial fluid was collected from multiple joints, cartilage was collected from the proximal surface of fused third and fourth metaca...
Bone Marrow MSC Secretome Increases Equine Articular Chondrocyte Collagen Accumulation and Their Migratory Capacities. Equine osteoarthritis (OA) leads to cartilage degradation with impaired animal well-being, premature cessation of sport activity, and financial losses. Mesenchymal stem cell (MSC)-based therapies are promising for cartilage repair, but face limitations inherent to the cell itself. Soluble mediators and extracellular vesicles (EVs) secreted by MSCs are the alternatives to overcome those limitations while preserving MSC restorative properties. The effect of equine bone marrow MSC secretome on equine articular chondrocytes (eACs) was analyzed with indirect co-culture and/or MSC-conditioned media ...
Conditioned serum in vitro treatment of chondrocyte pellets and osteoarthritic explants. Autologous conditioned serum (ACS) is used to treat osteoarthritis in horses, although its effects are not fully investigated. Objective: To investigate the effects of equine serum and conditioned serum on chondrocytes stimulated with interleukin (IL)-1β and cartilage explants with mild osteoarthritis. Methods: In vitro experimental study. Methods: The effect of three different serum preparations (unincubated control [PS], serum incubated 24 h [PS24h], and serum incubated 24 h in ACS containers [PCS]) pooled from lame horses were tested in two in vitro models. IL-1β and IL-1 receptor antagon...
Polyacrylamide hydrogel lubricates cartilage after biochemical degradation and mechanical injury. Intra-articular injections of hyaluronic acid have been a mainstay of osteoarthritis treatment for decades. However, controversy surrounds the mechanism of action and efficacy of this therapy. As such, there has been recent interest in developing synthetic lubricants that lubricate cartilage. Recently, a synthetic 4 wt% polyacrylamide (pAAm) hydrogel was shown to effectively decrease lameness in horses. However, its mechanism of action and ability to lubricate cartilage is unknown. The goal of this study was to characterize the lubricating ability of this hydrogel and determine its efficacy ...