English
French
Journal of orthopaedic research : official publication of the Orthopaedic Research Society.
Publisher:
Raven Press,. Hoboken, NJ : Wiley (2006)
Frequency: Bimonthly, 1989-
Country: United States
Language: English
Author(s):
Bioelectric Repair and Growth Society., Orthopaedic Research Society.
Start Year:1983 -
ISSN:
0736-0266 (Print)
1554-527X (Electronic)
0736-0266 (Linking)
1554-527X (Electronic)
0736-0266 (Linking)
Impact Factor
2.8
2022
| NLM ID: | 8404726 |
| (DNLM): | J33365000(s) |
| (OCoLC): | 09069401 |
| Coden: | JOREDR |
| LCCN: | sn 82008603 |
| Classification: | W1 JO804SF |
3D T1 relaxation time measurements in an equine model of subtle post-traumatic osteoarthritis using MB-SWIFT. The aim of this study is to assess whether articular cartilage changes in an equine model of post-traumatic osteoarthritis (PTOA), induced by surgical creation of standard (blunt) grooves, and very subtle sharp grooves, could be detected with ex vivo T relaxation time mapping utilizing three-dimensional (3D) readout sequence with zero echo time. Grooves were made on the articular surfaces of the middle carpal and radiocarpal joints of nine mature Shetland ponies and osteochondral samples were harvested at 39 weeks after being euthanized under respective ethical permissions. T relaxation times ...
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...
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 ...
Exercise history predicts focal differences in bone volume fraction, mineral density and microdamage in the proximal sesamoid bones of Thoroughbred racehorses. Medial proximal sesamoid bones (PSBs) from Thoroughbred racehorses that did (Case) or did not (Control) experience unilateral biaxial PSB fracture were evaluated for bone volume fraction (BVF), apparent mineral density (AMD), tissue mineral density (TMD), and microdamage in Case fractured, Case contralateral limb intact, and Control bones. A majority of Case bones had a subchondral lesion with high microdamage density, and low BVF, AMD, and TMD. Lesion microdamage and densitometric measures were associated with training history by robust linear regression. Exercise intensity was negatively rel...
Surface topography as a tool to detect early changes in a posttraumatic equine model of osteoarthritis. The equine model of posttraumatic osteoarthritis (OA) mimics certain aspects of the naturally occurring disease, both in horses and humans. The objective of this study was to assess articular cartilage degeneration in a posttraumatic OA model using the established macroscopic and microscopic scoring systems and compare them with a novel surface topography analysis. OA was induced in the carpal joint of 15 (n = 15) mixed breed horses. Surface changes on the articular cartilage were characterized using osteochondral blocks from the third carpal bone (C3) and radial carpal bone using surface...
Gene expression analysis of subchondral bone, cartilage, and synovium in naturally occurring equine palmar/plantar osteochondral disease. Osteoarthritis (OA) is a disease of the entire joint but the relationship between pathological events in various joint tissues is poorly understood. We examined concurrent changes in bone, cartilage, and synovium in a naturally occurring equine model of joint degeneration. Joints (n = 64) were grossly assessed for palmar/plantar osteochondral disease (POD) in racehorses that required euthanasia for unrelated reasons and assigned a grade of 0 (n = 34), 1 (n = 17), 2 or 3 (n = 13) using a recognized grading scheme. Synovium, cartilage, and subchondral bone were collected for hist...
Recombinant fibroblast growth factor-18 (sprifermin) enhances microfracture-induced cartilage healing. Posttraumatic osteoarthritis is a disabling condition impacting the mostly young and active population. In the present study, we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. For this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 μg) or with saline, hyaluronan, and evaluated a...
Dual-contrast computed tomography enables detection of equine posttraumatic osteoarthritis in vitro. To prevent the progression of posttraumatic osteoarthritis, assessment of cartilage composition is critical for effective treatment planning. Posttraumatic changes include proteoglycan (PG) loss and elevated water content. Quantitative dual-energy computed tomography (QDECT) provides a means to diagnose these changes. Here, we determine the potential of QDECT to evaluate tissue quality surrounding cartilage lesions in an equine model, hypothesizing that QDECT allows detection of posttraumatic degeneration by providing quantitative information on PG and water contents based on the partitions of...
“One Health” in tendinopathy research: Current concepts. Tendinopathy remains one of the most common musculoskeletal disorders affecting both human and equine athletes and presents a considerable therapeutic challenge. The following workshop report comes from the third Dorothy Havemeyer Symposium of Tendinopathy which provided a unique overview of our current understanding of both the basic science and the clinical challenges for diagnosing and treating tendinopathy in both species. Pathologically, tendon demonstrates alterations in both cellular, molecular, structural, and biomechanical features, leading to a spectrum of pathological endotypes. To ...
Structural, compositional, and functional effects of blunt and sharp cartilage damage on the joint: A 9-month equine groove model study. This study aimed to quantify the long-term progression of blunt and sharp cartilage defects and their effect on joint homeostasis and function of the equine carpus. In nine adult Shetland ponies, the cartilage in the radiocarpal and middle carpal joint of one front limb was grooved (blunt or sharp randomized). The ponies were subjected to an 8-week exercise protocol and euthanized at 39 weeks. Structural and compositional alterations in joint tissues were evaluated in vivo using serial radiographs, synovial biopsies, and synovial fluid samples. Joint function was monitored by quantitative gait...
Cationic contrast-enhanced computed tomography distinguishes between reparative, degenerative, and healthy equine articular cartilage. Cationic contrast-enhanced computed tomography (CECT) is a quantitative imaging technique that characterizes articular cartilage, though its efficacy in differentiating repair tissue from other disease states is undetermined. We hypothesized that cationic CECT attenuation will distinguish between reparative, degenerative, and healthy equine articular cartilage and will reflect biochemical, mechanical, and histologic properties. Chondral defects were created in vivo on equine femoropatellar joint surfaces. Within defects, calcified cartilage was retained (Repair 1) or removed (Repair 2). At sac...
Evaluation of articular cartilage with quantitative MRI in an equine model of post-traumatic osteoarthritis. Chondral lesions lead to degenerative changes in the surrounding cartilage tissue, increasing the risk of developing post-traumatic osteoarthritis (PTOA). This study aimed to investigate the feasibility of quantitative magnetic resonance imaging (qMRI) for evaluation of articular cartilage in PTOA. Articular explants containing surgically induced and repaired chondral lesions were obtained from the stifle joints of seven Shetland ponies (14 samples). Three age-matched nonoperated ponies served as controls (six samples). The samples were imaged at 9.4 T. The measured qMRI parameters included ...
T2* mapping in an equine articular groove model: Visualizing changes in collagen orientation. T2* mapping is promising for the evaluation of articular cartilage collagen. In this work, a groove model in a large animal is used as a model for posttraumatic arthritis. We hypothesized that T2* mapping could be employed to differentiate between healthy and (subtly) damaged cartilage. Eight carpal joints were obtained from four adult Shetland ponies that had been included in the groove study. In this model, grooves were surgically created on the proximal articular surface of the intermediate carpal bone (radiocarpal joint) and the radial facet of the third carpal bone (middle carpal joint) b...
Synovial fluid lubricin and hyaluronan are altered in equine osteochondral fragmentation, cartilage impact injury, and full-thickness cartilage defect models. The objectives of this study were to evaluate temporal changes in lubricin, hyaluronan (HA), and HA molecular weight (MW) distributions in three distinct models of equine joint injury affecting the carpal (wrist), tarsal (ankle), and femoropatellar (knee) joints. To establish ranges for lubricin, HA, and HA MW distributions across multiple joints, we first evaluated clinically healthy, high-motion equine joints. Synovial fluid was collected from high-motion joints in horses without clinical signs of joint disease (n = 11 horses, 102 joints) and from research horses undergoing carpal osteo...
Platelet-rich plasma lysate displays antibiofilm properties and restores antimicrobial activity against synovial fluid biofilms in vitro. Infectious arthritis is difficult to treat in both human and veterinary clinical practice. Recent literature reports Staphylococcus aureus as well as other gram-positive and gram-negative isolates forming free-floating biofilms in both human and equine synovial fluid that are tolerant to traditional antimicrobial therapy. Using an in vitro equine model, we investigated the ability of platelet-rich plasma (PRP) formulations to combat synovial fluid biofilm aggregates. Synovial fluid was infected, and biofilm aggregates allowed to form over a 2-hour period. PRP was collected and processed into d...
Contrast-Enhanced Computed Tomography Scoring System for Distinguishing Early Osteoarthritis Disease States: A Feasibility Study. Early detection of osteoarthritis (OA) remains a diagnostic challenge owing to insensitive diagnostic techniques currently available. Herein a new semiquantitative scoring system, based upon contrast-enhanced computed tomographic (CECT) imaging, is described for further refinement of early OA disease staging. Trochlear ridge cartilage defects were surgically created in the femoropatellar joint of an adult horse (ACUC approved protocols). Seven weeks post-surgery, CECT imaging was performed on a clinical scanner after intra-articular injection of a cationic iodinated contrast agent, CA4+, into ...
Urinary Bladder Matrix Does Not Improve Tenogenesis in an In Vitro Equine Model. Extracellular matrix (ECM) is responsible for tendon strength and elasticity. Healed tendon ECM lacks structural integrity, leading to reinjury. Porcine urinary bladder matrix (UBM) provides a scaffold and source of bioactive proteins to improve tissue healing, but has received limited attention for treating tendon injuries. The objective of this study was to evaluate the ability of UBM to induce matrix organization and tenogenesis using a novel in vitro model. We hypothesized that addition of UBM to tendon ECM hydrogels would improve matrix organization and cell differentiation. Hydrogels se...
Urinary bladder matrix does not improve tenogenesis in an in vitro equine model. Extracellular matrix (ECM) is responsible for tendon strength and elasticity. Healed tendon ECM lacks structural integrity, leading to reinjury. Porcine urinary bladder matrix (UBM) provides a scaffold and source of bioactive proteins to improve tissue healing, but has received limited attention for treating tendon injuries. The objective of this study was to evaluate the ability of UBM to induce matrix organization and tenogenesis using a novel in vitro model. We hypothesized that addition of UBM to tendon ECM hydrogels would improve matrix organization and cell differentiation. Hydrogels see...
Adipose-Derived Stromal Vascular Fraction and Cultured Stromal Cells as Trophic Mediators for Tendon Healing. Adipose-derived stromal vascular fraction (SVF) is a heterogeneous population of cells that yields a homogeneous population of plastic-adherent adipose tissue-derived stromal cells (ASC) when culture-expanded. SVF and ASC have been used clinically to improve tendon healing, yet their mechanism of action is not fully elucidated. The objective of this study was to investigate the potential for ASC to act as trophic mediators for tendon healing. Flexor digitorum superficialis tendons and adipose tissue were harvested from adult horses to obtain SVF, ASC, and tenocytes. Growth factor gene expressi...
Temporal changes in synovial fluid composition and elastoviscous lubrication in the equine carpal fracture model. The objective of this study was to examine temporal variations in synovial fluid composition and lubrication following articular fracture. Post-traumatic osteoarthritis (PTOA) was induced by creating an osteochondral fracture in the middle carpal joint of four horses while the contralateral limb served as a sham-operated control. Horses were exercised on a high-speed treadmill, and synovial fluid was collected pre-operatively and at serial timepoints until 75 days post-operatively. Lubricin and hyaluronic acid (HA) concentrations were measured using sandwich ELISAs, and the molecular weight di...
Genetic modification of scAAV-equine-BMP-2 transduced bone-marrow-derived mesenchymal stem cells before and after cryopreservation: An “off-the-shelf” option for fracture repair. Optimizing the environment of complex bone healing and improving treatment of catastrophic bone fractures and segmental bone defects remains an unmet clinical need both human and equine veterinary medical orthopaedics. The objective of this study was to determine whether scAAV-equine-BMP-2 transduced cells would induce osteogenesis in equine bone marrow derived mesenchymal stem cells (BMDMSCs) in vitro, and if these cells could be cryopreserved in an effort to osteogenically prime them as an "off-the-shelf" gene therapeutic approach for fracture repair. Our study found that transgene expressio...
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 ...
Interaction with macrophages attenuates equine fibroblast-like synoviocyte ADAMTS5 (aggrecanase-2) gene expression following inflammatory stimulation. The joint synovium consists of a heterogeneous cell population, chiefly comprised of macrophages, and fibroblast-like synoviocytes (FLS). An inter-species co-culture model was developed to examine interactions between these cells. Equine FLS and the canine macrophage line DH82 were differentially labeled using fluorescent markers and results from direct co-culture compared with those from both indirect co-culture, and conditioned media experiments. The transcript expression of IL-1β, IL-6, ADAMTS4, and ADAMTS5 in each cell type were determined using species-specific qPCR assays. Lipopolysacch...
Biomarkers for equine joint injury and osteoarthritis. 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...
Modulating the oxidative environment during mesenchymal stem cells chondrogenesis with serum increases collagen accumulation in agarose culture. Chondrogenesis of mesenchymal stem cells (MSCs) is induced in culture conditions that have been associated with oxidative stress, although the extent to which the oxidative environment affects differentiation and extracellular matrix (ECM) accumulation is not known. The objectives of this study were to evaluate the oxidative environment during MSCs chondrogenesis in conventional serum-free medium, and the effect of serum-supplementation on intracellular reactive oxygen species (ROS) and chondrogenesis. Young adult equine MSCs were seeded into agarose and cultured in chondrogenic medium, with o...
Tendon-derived progenitor cells improve healing of collagenase-induced flexor tendinitis. Tendinitis is a common and a performance-limiting injury in athletes. This study describes the value of intralesional tendon-derived progenitor cell (TDPC) injections in equine flexor tendinitis. Collagenase-induced tendinitis was created in both front superficial digital flexor (SDF) tendons. Four weeks later, the forelimb tendon lesions were treated with 1 × 10 autogenous TDPCs or saline. Tendinitis was also induced by collagenase in one hind SDF tendon, to study the survival and distribution of DiI-labeled TDPCs 1, 2, 4, and 6 weeks after injection. The remaining normal tendon was used...
Femoral epiphyseal cartilage matrix changes at predilection sites of equine osteochondrosis: Quantitative MRI, second-harmonic microscopy, and histological findings. Osteochondrosis is an ischemic chondronecrosis of epiphyseal growth cartilage that results in focal failure of endochondral ossification and osteochondritis dissecans at specific sites in the epiphyses of humans and animals, including horses. The upstream events leading to the focal ischemia remain unknown. The epiphyseal growth cartilage matrix is composed of proteoglycan and collagen macromolecules and encases its vascular tree in canals. The matrix undergoes major dynamic changes in early life that could weaken it biomechanically and predispose it to focal trauma and vascular failure. Subre...
Differences in the vascular tree of the femoral trochlear growth cartilage at osteochondrosis-susceptible sites in foals revealed by SWI 3T MRI. Focal ischemic chondronecrosis of epiphyseal growth cartilage (EGC) during endochondral ossification is believed to be a key early event on the pathway to osteochondrosis (OC) in both animals and humans. The lateral ridge of the equine trochlea is a site where severe osteochondritis dissecans lesions frequently arise and is a model for the study of naturally occurring disease. Non-invasive imaging to investigate EGC vascularity may help elucidate why focal ischemia occurs. 3T MRI susceptibility-weighted imaging (SWI) of femoral trochlea of OC predisposed (n = 10) and control (n = 6) da...
Identification of novel osteochondrosis–Associated genes. During the early stages of articular osteochondrosis, cartilage is retained in subchondral bone, but the pathophysiology of this condition of growing humans and domestic animals is poorly understood. A subtractive hybridization study was undertaken to compare gene expression between the cartilage of early experimentally induced equine osteochondrosis lesions and control cartilage. Of the many putative differentially expressed genes identified, eight were confirmed by quantitative PCR analysis as differentially expressed, in addition to those already known to be associated with early lesions. G...
Mechanical properties and structure-function relationships in articular cartilage repaired using IGF-I gene-enhanced chondrocytes. Several studies have demonstrated the benefits of IGF-I gene therapy in enhancing the histologic and biochemical content of cartilage repaired by chondrocyte transplantation. However, there is little to no data on the mechanical performance of IGF-I augmented cartilage grafts. This study evaluated the compressive properties of full-thickness chondral defects in the equine femur repaired with and without IGF-I gene therapy. Animals were randomly assigned to one of three study cohorts based on chondrocyte treatment provided in each defect: (i) IGF-I gene delivered by recombinant adeno-associated...
