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Laurie R. Goodrich - One of the best experts on this subject based on the ideXlab platform.
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Use of in vitro assays to identify antibiotics that are cytotoxic to normal Equine chondrocytes and synovial cells.
Equine veterinary journal, 2020Co-Authors: Lynn Pezzanite, Lyndah Chow, Gabriella Piquini, Gregg Griffenhagen, Dominique Ramirez, Steven W. Dow, Laurie R. GoodrichAbstract:BACKGROUND Intra-articular (IA) antibiotic usage is prevalent in Equine practice. However, recent emergence of antimicrobial resistance prompts re-evaluation of antibiotic selection, particularly when used prophylactically. Furthermore, many commonly used antibiotics exert direct cytotoxicity to Equine cells, and appropriate IA doses have not been defined. OBJECTIVES To screen antibiotics in vitro as an initial assessment of cytotoxicity against normal Equine Joint cells in monolayer culture and explant tissues. STUDY DESIGN In vitro experimental study. METHODS Chondrocytes and synovial cells were harvested from three horses and plated on 24-well plates (100 000 cells/wells in triplicate) for 48 hours prior to addition of antibiotics. Joint cells were exposed to antibiotics (n = 15) at various doses (25-0.39 mg/mL in complete DMEM media) for 24 hours and viability was assessed by trypan blue dye exclusion. The half maximal inhibitory concentration (IC50) was determined for each antibiotic. Cartilage explants were obtained from 3 horses, minced and exposed to antibiotics (n = 5) for 72 hours. Live/dead staining was performed, and fluorescence was visualised using Olympus IX83 spinning disk confocal microscope. Percentage of live vs dead cells was quantified. RESULTS Antibiotics from different antimicrobial classes expressed dose-dependent but variable cytotoxicity to Equine Joint cells in vitro. Aminoglycosides and doxycycline had the lowest IC50 (most toxic). Ampicillin sulbactam, imipenem, tobramycin, ceftiofur sodium and amoxicillin had IC50 > 25 mg/mL for at least one cell line, representing potentially less cytotoxic alternatives. MAIN LIMITATIONS Further studies are necessary to extrapolate these in vitro data results to the in vivo Joint environment. CONCLUSIONS Targeted IA antibiotic therapy would involve selection of the safest antibiotics (highest IC50) with efficacy based on bacterial culture/sensitivity. Antimicrobial selection and evidence-based dosing may minimise damage to native articular cartilage and synovial cells and development of antimicrobial resistance when IA antibiotics are used in Equine practice.
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Amikacin induces rapid dose-dependent apoptotic cell death in Equine chondrocytes and synovial cells in vitro.
Equine veterinary journal, 2020Co-Authors: Lynn Pezzanite, Lyndah Chow, Laurie R. Goodrich, Sirikul Soontararak, Jennifer N. Phillips, Steven W. DowAbstract:BACKGROUND: Equine veterinarians frequently inject aminoglycoside antibiotics intra‐articularly, either to treat septic arthritis or for prophylaxis with other medications when injecting Joints for osteoarthritis. Although aminoglycosides have been demonstrated to be toxic to Equine mesenchymal stem cells (MSC), their effects on resident Joint cells have not been previously investigated. Moreover, safe and effective intra‐articular doses have not been defined. OBJECTIVES: To determine effects of concentration, duration of exposure, pH and the presence of synovial fluid on the cytotoxic effects of amikacin on Equine chondrocytes, synoviocytes and bone marrow– and adipose‐derived MSC. STUDY DESIGN: In vitro experimental study. METHODS: Four cell types were harvested from three donor horses and plated in triplicate wells for 48 hours prior to the addition of amikacin. The effects of amikacin on cell viability were assessed for different exposure times, concentrations and with pH buffered or unbuffered in media, as well as in the presence of synovial fluid. Cell metabolism/viability was assessed by colorimetric MTT assay. Cell proliferation was assessed by live cell imaging. Cell viability was assessed using trypan blue and dimeric cyanine nucleic acid stain (yoyo‐1). To determine the mechanism of cell death, apoptosis was evaluated using Annexin V and 7AAD staining with flow cytometric quantification. Induction of apoptotic cell death pathways was assessed using caspase‐3 expression. RESULTS: Amikacin is cytotoxic to Equine Joint cells and MSC in a rapid, dose‐dependent, pH‐independent manner, which occurs primarily by apoptosis. Amikacin cytotoxicity was not mitigated by the addition of synovial fluid in vitro. MAIN LIMITATIONS: Further studies are necessary to determine whether these in vitro results predict Joint injury in live animal models. CONCLUSIONS: Amikacin at clinically applied doses induces rapid, pronounced cell death of Equine Joint cells. These findings suggest that amikacin doses currently used intra‐articularly should be reconsidered pending in vivo Joint titration studies.
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Adeno-Associated Viral Vectors Show Serotype Specific Transduction of Equine Joint Tissue Explants and Cultured Monolayers
Scientific Reports, 2014Co-Authors: Daniel D. Hemphill, C Wayne Mcilwraith, R. Jude Samulski, Laurie R. GoodrichAbstract:Adeno-associated virus (AAV) receptors range from heparan sulfate proteoglycan to sialic acid moieties present on cell surfaces. Abundance of the glycan profiles is greatly influenced by animal species, cell type and culture conditions. The objective of this study was to determine whether AAV serotypes' transduction efficiencies specifically in the Equine monolayer culture model are an accurate representation of transduction efficiencies in tissue explants, a model more closely related to in vivo transduction. It was found that AAV 2 and 2.5 transduced cells more efficiently in explants than in monolayers. Through experiments involving assessing enzyme degradation of cell surface proteoglycans, this change could not be attributed to differences in the extra cellular matrix (ECM), but a similar change in AAV 5 transduction efficiency could be readily explained by differences in cell surface sialylated glycan. Unexpectedly it was found that in a small but diverse sample of horses evidence for serum neutralizing antibodies was only found to AAV 5. This suggests a unique relationship between this capsid and the Equine host or an unresolved relationship between similar bovine AAV and the AAV 5 capsid immune response.
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Ex Vivo Serotype-Specific Transduction of Equine Joint Tissue by Self-Complementary Adeno-Associated Viral Vectors
Human gene therapy, 2009Co-Authors: Laurie R. Goodrich, C. W. Mcilwraith, V.w. Choi, B.a. Duda Carbone, R. Jude SamulskiAbstract:Cell transplantation for the treatment of Joint disease is an important clinical tool. Genetic modification of cells before transplantation has shown enhanced healing. Ex vivo genetic modification of Joint tissue cells with various adeno-associated virus (AAV) serotypes has not been investigated. The transduction efficiencies of self-complementary AAV serotypes (1-6 and 8) were determined in Joint tissue containing chondrocytes and synoviocytes isolated from Equine models. When comparing scAAV serotypes for efficient transduction ex vivo, in chondrocytes versus synoviocytes, serotypes 6 and 2, and serotypes 3 and 2, respectively, appeared superior for gene expression. Unlike adenoviral vectors, no upregulation of inflammatory markers, such as matrix metalloproteinases and aggrecanase, was seen on treatment of Joint tissue with AAV vectors ex vivo. Our findings also corroborate that ex vivo transduction of Joint tissue can result in high transgene protein levels over time, and transplantation modalities might be feasible using AAV vectors in the treatment of Joint-related diseases.
R. Jude Samulski - One of the best experts on this subject based on the ideXlab platform.
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Adeno-Associated Viral Vectors Show Serotype Specific Transduction of Equine Joint Tissue Explants and Cultured Monolayers
Scientific Reports, 2014Co-Authors: Daniel D. Hemphill, C Wayne Mcilwraith, R. Jude Samulski, Laurie R. GoodrichAbstract:Adeno-associated virus (AAV) receptors range from heparan sulfate proteoglycan to sialic acid moieties present on cell surfaces. Abundance of the glycan profiles is greatly influenced by animal species, cell type and culture conditions. The objective of this study was to determine whether AAV serotypes' transduction efficiencies specifically in the Equine monolayer culture model are an accurate representation of transduction efficiencies in tissue explants, a model more closely related to in vivo transduction. It was found that AAV 2 and 2.5 transduced cells more efficiently in explants than in monolayers. Through experiments involving assessing enzyme degradation of cell surface proteoglycans, this change could not be attributed to differences in the extra cellular matrix (ECM), but a similar change in AAV 5 transduction efficiency could be readily explained by differences in cell surface sialylated glycan. Unexpectedly it was found that in a small but diverse sample of horses evidence for serum neutralizing antibodies was only found to AAV 5. This suggests a unique relationship between this capsid and the Equine host or an unresolved relationship between similar bovine AAV and the AAV 5 capsid immune response.
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Ex Vivo Serotype-Specific Transduction of Equine Joint Tissue by Self-Complementary Adeno-Associated Viral Vectors
Human gene therapy, 2009Co-Authors: Laurie R. Goodrich, C. W. Mcilwraith, V.w. Choi, B.a. Duda Carbone, R. Jude SamulskiAbstract:Cell transplantation for the treatment of Joint disease is an important clinical tool. Genetic modification of cells before transplantation has shown enhanced healing. Ex vivo genetic modification of Joint tissue cells with various adeno-associated virus (AAV) serotypes has not been investigated. The transduction efficiencies of self-complementary AAV serotypes (1-6 and 8) were determined in Joint tissue containing chondrocytes and synoviocytes isolated from Equine models. When comparing scAAV serotypes for efficient transduction ex vivo, in chondrocytes versus synoviocytes, serotypes 6 and 2, and serotypes 3 and 2, respectively, appeared superior for gene expression. Unlike adenoviral vectors, no upregulation of inflammatory markers, such as matrix metalloproteinases and aggrecanase, was seen on treatment of Joint tissue with AAV vectors ex vivo. Our findings also corroborate that ex vivo transduction of Joint tissue can result in high transgene protein levels over time, and transplantation modalities might be feasible using AAV vectors in the treatment of Joint-related diseases.
C. W. Mcilwraith - One of the best experts on this subject based on the ideXlab platform.
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Joint disease in the horse [2nd Ed.]
2015Co-Authors: C. W. Mcilwraith, G.w. TrotterAbstract:General Principles of Joint Pathobiology General Anatomy and Physiology of Joints Joint Functions Types of Joints Embryonic Joint Development Principles of Joint Anatomy Principles of Joint Physiology Conclusions References Biomechanics in Joints Biomechanical Considerations that Influence Joint Disease References Traumatic Arthritis and Posttraumatic Osteoarthritis in the Horse Traumatic Arthritis References Pathologic Manifestations of Joint Disease Pathogenesis of Joint Disease Biomechanical Influences on Joint Disease Summary References Osteochondritis Dissecans History and Terminology The Process of Endochondral Ossiication Clinical Presentation of Oc Prevalence and Evolution of Osteochondrosis The Pathophysiologic Mechanism behind Osteochondrosis Etiologic Factors Treatment Prognosis Economic and Welfare Impact of Osteochondrosis Conclusion and Pointers for Further Research References Subchondral Cystic Lesions Subchondral Cystic Lesions Pathogenesis Summary References Septic Arthritis Pathophysiology Etiology and Causative Organisms Epidemiology Clinical Signs and Diagnosis Treatment Joint Lavage or Drainage Prognosis Septic Arthritis in Foals Conclusion References Effects of Loading/Exercise on Articular Tissues and Developmental Aspects of Joints Loading of the Mature Joint: Balancing between Maintenance and Morbidity Loading of the Juvenile Joint: Crucial Conditioning Conclusion References General Principles of Diagnosis and Treatment Principles of Diagnosis Clinical Examination Principles of Imaging References Synovial Fluid and Serum Biomarkers What is a Biomarker? Understanding Joint Structure and Metabolism in Health and Disease Individual Direct Biomarkers of Articular Cartilage Metabolism in Osteoarthritis Individual Direct Biomarkers of Bone Metabolism in Joint Disease Indirect Biomarkers of Joint Homeostasis Future of Biomarkers in Osteoarthritis References Principles of Therapy of Traumatic Arthritis and Osteoarthritis Nonsteroidal Antiinflammatory Drugs, 192 Specific Uses of Nsaids What are the Negative Effects with Use of Nsaids? Potential Analgesic Effects of Nsaids with Regard to Withdrawal from Competition References Intraarticular Corticosteroids Early History of Corticosteroid Use in Equine Joint Disease Early Evaluations of Direct Effects More Recent Research on Beneficial and Deleterious Effects in in Vivo and in Vitro Equine Models Can Adjunctive Use of Hyaluronan in Conjunction with Methylprednisolone Acetonide Mitigate the Deleterious Effects? Combined Use of Hyaluronan and Triamcinolone Acetonide Laminitis: A Suggested Potential Complication of Intraarticular Corticosteroid Use What are Equine Veterinarians Using in Practice? The Association of Intraarticular Corticosteroids and Catastrophic Injury Pharmacology of Corticosteroids and Duration of Pharmacologic Effects Clinical Effectiveness (PHARMACODYNAMICS) Relative to Pharmacologic Presence (PHARMACOKINETICS) and Potential to Quantitate this Activity The Influence of Rest from Exercise after Intraarticular Corticosteroid Injection An Evolution of Stricter Drug Restrictions Summary References Hyaluronan Role of Hyaluronan in Joint Disease Summary References Polysulfated Glycosaminoglycan (Adequan?) Early Studies in in Vitro and in Vivo Models Clinical Use and More Recent Evidence for Efficacy Hyaluronan, Sodium Chondroitin Sulfate, and N-Acetyl-d-Glucosamine Combination Products References Pentosan Polysulfate Mechanisms of Action Studies in Horses Summary References Biologic Therapies Autologous Conditioned Serum Platelet-Rich Plasma Summary References Stem Cells Choice of Source for Mesenchymal Stem Cells Dose of Mesenchymal Stem Cells Timing and Number of Treatments with Mesenchymal Stem Cells Cartilage Injury/Focal Resurfacing Osteoarthritis Intraarticular Soft Tissue Injuries Summary References Physical Rehabilitation Rehabilitation Issues in Joint Disease Pain and Inflammation Proprioception and Joint Instability Joint Stiffness Neuromuscular Control Endurance and Strength Use of Aquatic Therapies in Managing Joint Disease Summary References Use of Oral Joint Supplements in Equine Joint Disease Indications for Oral Joint Supplements Terminology and Regulatory Issues in the Use of Oral Joint Supplements (a U.S. Perspective) Types of Oral Joint Supplements Summary References Specifics of Anatomy, Clinical Diagnosis, Imaging Diagnosis, and Treatment by Region Distal Limb Distal Interphalangeal Joint Pathologic Change in the Distal Interphalangeal Joint Proximal Interphalangeal Joint References Fetlock Anatomy Diagnostic Imaging of the Equine Fetlock References Carpus Imaging Parameters Clinical Signs Specific Conditions References The Elbow and Shoulder Elbow Shoulder References Tarsus Imaging Parameters Clinical Signs Specific Conditions References Stifle Diagnostic Imaging of the Stile Specific Conditions References The Hip Radiography Ultrasound Nuclear Scintigraphy Osteoarthritis Osteochondrosis/Hip Dysplasia Fractures/Luxation Septic Arthritis References New Frontiers Equine Joint Disease: Present and Future Directions in Research (EARLY) Diagnosis of Joint Disease Therapies (Both Symptom-Modifying and Disease-Modifying) Articular Cartilage Healing (REPAIR) Improvement in the Understanding of Pathogenesis of Exercise-Induced Traumatic Disease Rehabilitation and Physical Therapy References
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Evidence supporting an increased presence of reactive oxygen species in the diseased Equine Joint.
Equine veterinary journal, 2010Co-Authors: A. N. Dimock, Paul D. Siciliano, C. W. McilwraithAbstract:Summary Reactive oxygen species (ROS) are capable of degrading many components of the Joint in the presence of insufficient antioxidant defences, and as a result have been implicated in the pathogenesis of Joint disease in horses. However, to our knowledge, evidence of ROS occurring in diseased Joints of horses has not been reported. The objective of this experiment was to compare differences in synovial fluid protein carbonyl content (as a marker of oxidative modification of synovial fluid proteins by ROS) and the antioxidant status of synovial fluid between clinically normal and diseased Equine Joints. Synovial fluid was collected from the metacarpophalangeal, metatarsophalangeal, carpal and tarsal Joints of 4 horses, age 2–5 years, as controls, and from diseased Joints (metacarpophalangeal, metatarsophalangeal, carpal, tarsal and/or femoropatellar) of 61 horses, age 2–5 years. Synovial fluid protein carbonyl content was higher (P
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evidence supporting an increased presence of reactive oxygen species in the diseased Equine Joint
Equine Veterinary Journal, 2010Co-Authors: A. N. Dimock, Paul D. Siciliano, C. W. McilwraithAbstract:Summary Reactive oxygen species (ROS) are capable of degrading many components of the Joint in the presence of insufficient antioxidant defences, and as a result have been implicated in the pathogenesis of Joint disease in horses. However, to our knowledge, evidence of ROS occurring in diseased Joints of horses has not been reported. The objective of this experiment was to compare differences in synovial fluid protein carbonyl content (as a marker of oxidative modification of synovial fluid proteins by ROS) and the antioxidant status of synovial fluid between clinically normal and diseased Equine Joints. Synovial fluid was collected from the metacarpophalangeal, metatarsophalangeal, carpal and tarsal Joints of 4 horses, age 2–5 years, as controls, and from diseased Joints (metacarpophalangeal, metatarsophalangeal, carpal, tarsal and/or femoropatellar) of 61 horses, age 2–5 years. Synovial fluid protein carbonyl content was higher (P<0.01) in diseased Joints as compared to controls. Antioxidant status of synovial fluid from diseased Joints was higher, but not significantly, than that of controls (P = 0.0595). These findings require further study to determine their contribution to the overall disease process.
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Ex Vivo Serotype-Specific Transduction of Equine Joint Tissue by Self-Complementary Adeno-Associated Viral Vectors
Human gene therapy, 2009Co-Authors: Laurie R. Goodrich, C. W. Mcilwraith, V.w. Choi, B.a. Duda Carbone, R. Jude SamulskiAbstract:Cell transplantation for the treatment of Joint disease is an important clinical tool. Genetic modification of cells before transplantation has shown enhanced healing. Ex vivo genetic modification of Joint tissue cells with various adeno-associated virus (AAV) serotypes has not been investigated. The transduction efficiencies of self-complementary AAV serotypes (1-6 and 8) were determined in Joint tissue containing chondrocytes and synoviocytes isolated from Equine models. When comparing scAAV serotypes for efficient transduction ex vivo, in chondrocytes versus synoviocytes, serotypes 6 and 2, and serotypes 3 and 2, respectively, appeared superior for gene expression. Unlike adenoviral vectors, no upregulation of inflammatory markers, such as matrix metalloproteinases and aggrecanase, was seen on treatment of Joint tissue with AAV vectors ex vivo. Our findings also corroborate that ex vivo transduction of Joint tissue can result in high transgene protein levels over time, and transplantation modalities might be feasible using AAV vectors in the treatment of Joint-related diseases.
C Wayne Mcilwraith - One of the best experts on this subject based on the ideXlab platform.
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Adeno-Associated Viral Vectors Show Serotype Specific Transduction of Equine Joint Tissue Explants and Cultured Monolayers
Scientific Reports, 2014Co-Authors: Daniel D. Hemphill, C Wayne Mcilwraith, R. Jude Samulski, Laurie R. GoodrichAbstract:Adeno-associated virus (AAV) receptors range from heparan sulfate proteoglycan to sialic acid moieties present on cell surfaces. Abundance of the glycan profiles is greatly influenced by animal species, cell type and culture conditions. The objective of this study was to determine whether AAV serotypes' transduction efficiencies specifically in the Equine monolayer culture model are an accurate representation of transduction efficiencies in tissue explants, a model more closely related to in vivo transduction. It was found that AAV 2 and 2.5 transduced cells more efficiently in explants than in monolayers. Through experiments involving assessing enzyme degradation of cell surface proteoglycans, this change could not be attributed to differences in the extra cellular matrix (ECM), but a similar change in AAV 5 transduction efficiency could be readily explained by differences in cell surface sialylated glycan. Unexpectedly it was found that in a small but diverse sample of horses evidence for serum neutralizing antibodies was only found to AAV 5. This suggests a unique relationship between this capsid and the Equine host or an unresolved relationship between similar bovine AAV and the AAV 5 capsid immune response.
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Transcriptional profiling differences for articular cartilage and repair tissue in Equine Joint surface lesions
BMC Medical Genomics, 2009Co-Authors: Michael J Mienaltowski, David D Frisbie, Liping Huang, Arnold J Stromberg, Arne C Bathke, C Wayne Mcilwraith, James N MacleodAbstract:Background Full-thickness articular cartilage lesions that reach to the subchondral bone yet are restricted to the chondral compartment usually fill with a fibrocartilage-like repair tissue which is structurally and biomechanically compromised relative to normal articular cartilage. The objective of this study was to evaluate transcriptional differences between chondrocytes of normal articular cartilage and repair tissue cells four months post-microfracture. Methods Bilateral one-cm^2 full-thickness defects were made in the articular surface of both distal femurs of four adult horses followed by subchondral microfracture. Four months postoperatively, repair tissue from the lesion site and grossly normal articular cartilage from within the same femorotibial Joint were collected. Total RNA was isolated from the tissue samples, linearly amplified, and applied to a 9,413-probe set Equine-specific cDNA microarray. Eight paired comparisons matched by limb and horse were made with a dye-swap experimental design with validation by histological analyses and quantitative real-time polymerase chain reaction (RT-qPCR). Results Statistical analyses revealed 3,327 (35.3%) differentially expressed probe sets. Expression of biomarkers typically associated with normal articular cartilage and fibrocartilage repair tissue corroborate earlier studies. Other changes in gene expression previously unassociated with cartilage repair were also revealed and validated by RT-qPCR. Conclusion The magnitude of divergence in transcriptional profiles between normal chondrocytes and the cells that populate repair tissue reveal substantial functional differences between these two cell populations. At the four-month postoperative time point, the relative deficiency within repair tissue of gene transcripts which typically define articular cartilage indicate that while cells occupying the lesion might be of mesenchymal origin, they have not recapitulated differentiation to the chondrogenic phenotype of normal articular chondrocytes.
David D Frisbie - One of the best experts on this subject based on the ideXlab platform.
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biomarkers for Equine Joint injury and osteoarthritis
Journal of Orthopaedic Research, 2018Co-Authors: Wayne C Mcilwraith, David D Frisbie, Christopher B Little, Christopher E Kawcak, P D Clegg, Mandy J Peffers, Morten A Karsdal, Stina Ekman, Sheila Laverty, Richard A SlaydenAbstract:We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of Joint injury leading to Equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bone failure in Equine athletes. The workshop was attended by leading scientists in the fields of Equine and human musculoskeletal biomarkers to enable cross-disciplinary exchange and improve knowledge in both. Detailed proceedings with strategic planning was written, added to, edited and referenced to develop this manuscript. The most recent information from work in Equine and human osteoarthritic biomarkers was accumulated, including the use of personalized healthcare to stratify OA phenotypes, transcriptome analysis of anterior cruciate ligament (ACL) and meniscal injuries in the human knee. The spectrum of "wet" biomarker assays that are antibody based that have achieved usefulness in both humans and horses, imaging biomarkers and the role they can play in Equine and human OA was discussed. Prediction of musculoskeletal injury in the horse remains a challenge, and the potential usefulness of spectroscopy, metabolomics, proteomics, and development of biobanks to classify biomarkers in different stages of Equine and human OA were reviewed. The participants concluded that new information and studies in Equine musculoskeletal biomarkers have potential translational value for humans and vice versa. OA is equally important in humans and horses, and the welfare issues associated with catastrophic musculoskeletal injury in horses add further emphasis to the need for good validated biomarkers in the horse. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:823-831, 2018.
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Cartilage Therapy and Repair in Equine Athletes
Operative Techniques in Orthopaedics, 2016Co-Authors: Sherry A. Johnson, David D FrisbieAbstract:The status of articular cartilage often defines the level, progression, and subsequent prognosis of Joint disease in both human and Equine athletes. Although methods to diagnose Equine cartilage defects have significantly improved over the past decade, articular cartilage damage and ensuing osteoarthritis remain a challenge to treat. The following 2 categories of surgical options for cartilage repair in the horse are typically considered: palliative and reparative or restorative. Palliative surgical care consists of arthroscopic debridement and lavage, whereas reparative options involve the use of marrow stimulation techniques. Restorative or reparative surgical options are an area of active research, including the use of osteochondral grafting, autologous chondrocyte implantation (ACI), and augmentation with mesenchymal stem cells (MSCs). Subchondral bone microfracture coupled with intra-articular stem cell injection is currently considered to be the optimal treatment combination for Equine patients with articular cartilage defects. Following arthroscopic surgery, the rehabilitative goals are to provide support to the affected limb, restore Joint flexibility, stability, and manage perioperative pain. In addition, biologic therapy for the treatment of Equine Joint disease continues to be clinically employed and of investigational interest. With the large amount of ongoing in vitro research in bioprinted osteochondral constructs and potential extracellular matrix components, and the advantages of the in vivo Equine model of articular cartilage repair as well as naturally occurring disease, it seems inevitable that the horse would be used to develop these novel techniques.
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Cell-based Therapies for Equine Joint Disease
Veterinary Clinics of North America-equine Practice, 2011Co-Authors: David D Frisbie, Matthew C. StewartAbstract:Joint disease is a major cause of wastage in performance horses. Arthritis can be challenging to treat because articular cartilage has little or no capacity for repair, therapeutic options are limited and are largely targeted at ameliorating clinical signs of Joint disease. Cell-based therapies have potential to overcome the intrinsic constraints to articular cartilage repair. This article focuses on cell-based therapies for treatment of Equine Joint disease. Results from experimental model and human clinical studies are presented along with available data from Equine studies.
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transcriptional profiling differences for articular cartilage and repair tissue in Equine Joint surface lesions
BMC Medical Genomics, 2009Co-Authors: Michael J Mienaltowski, David D Frisbie, Wayne C Mcilwraith, Liping Huang, Arnold J Stromberg, Arne C Bathke, James N MacleodAbstract:Background Full-thickness articular cartilage lesions that reach to the subchondral bone yet are restricted to the chondral compartment usually fill with a fibrocartilage-like repair tissue which is structurally and biomechanically compromised relative to normal articular cartilage. The objective of this study was to evaluate transcriptional differences between chondrocytes of normal articular cartilage and repair tissue cells four months post-microfracture.
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Transcriptional profiling differences for articular cartilage and repair tissue in Equine Joint surface lesions
BMC Medical Genomics, 2009Co-Authors: Michael J Mienaltowski, David D Frisbie, Liping Huang, Arnold J Stromberg, Arne C Bathke, C Wayne Mcilwraith, James N MacleodAbstract:Background Full-thickness articular cartilage lesions that reach to the subchondral bone yet are restricted to the chondral compartment usually fill with a fibrocartilage-like repair tissue which is structurally and biomechanically compromised relative to normal articular cartilage. The objective of this study was to evaluate transcriptional differences between chondrocytes of normal articular cartilage and repair tissue cells four months post-microfracture. Methods Bilateral one-cm^2 full-thickness defects were made in the articular surface of both distal femurs of four adult horses followed by subchondral microfracture. Four months postoperatively, repair tissue from the lesion site and grossly normal articular cartilage from within the same femorotibial Joint were collected. Total RNA was isolated from the tissue samples, linearly amplified, and applied to a 9,413-probe set Equine-specific cDNA microarray. Eight paired comparisons matched by limb and horse were made with a dye-swap experimental design with validation by histological analyses and quantitative real-time polymerase chain reaction (RT-qPCR). Results Statistical analyses revealed 3,327 (35.3%) differentially expressed probe sets. Expression of biomarkers typically associated with normal articular cartilage and fibrocartilage repair tissue corroborate earlier studies. Other changes in gene expression previously unassociated with cartilage repair were also revealed and validated by RT-qPCR. Conclusion The magnitude of divergence in transcriptional profiles between normal chondrocytes and the cells that populate repair tissue reveal substantial functional differences between these two cell populations. At the four-month postoperative time point, the relative deficiency within repair tissue of gene transcripts which typically define articular cartilage indicate that while cells occupying the lesion might be of mesenchymal origin, they have not recapitulated differentiation to the chondrogenic phenotype of normal articular chondrocytes.