A5046760426- Osteoarthritis Treatment and Mechanisms
- Spine and Intervertebral Disc Pathology
- Musculoskeletal pain and rehabilitation
- Proteoglycans and glycosaminoglycans research
- Shoulder Injury and Treatment
- Fibroblast Growth Factor Research
- Tendon Structure and Treatment
- Total Knee Arthroplasty Outcomes
- Cervical and Thoracic Myelopathy
- Connective tissue disorders research
- Knee injuries and reconstruction techniques
- Peptidase Inhibition and Analysis
- Immune Response and Inflammation
- Medical Imaging and Analysis
- Rheumatoid Arthritis Research and Therapies
- Inflammatory mediators and NSAID effects
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Bee Products Chemical Analysis
- Bone fractures and treatments
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Plant Toxicity and Pharmacological Properties
- Periodontal Regeneration and Treatments
- Exercise and Physiological Responses
- Pregnancy-related medical research
Royal North Shore Hospital
2013-2024
The University of Sydney
2013-2023
Northern Sydney Local Health District
2015-2020
Keogh Institute for Medical Research
2019
UNSW Sydney
2016
Longitudinal case-controlled animal study.To investigate putative cellular mechanisms to explain structural changes in muscle and adipose connective tissues of the back muscles after intervertebral disc (IVD) injury.Structural are ubiquitous with pain/injury considered relevant for outcome, but their exact nature, time course, remain elusive. We used an model that produces phenotypic IVD injury study these issues at cellular/molecular level.Multifidus was harvested from both sides spine...
Longitudinal case-controlled animal study.To investigate the effect of an intervertebral disc (IVD) lesion on proportion slow, fast, and intermediate muscle fiber types in multifidus sheep, whether changes were paralleled by local gene expression proinflammatory cytokines tumor necrosis factor α (TNF-α) interleukin 1-β.Structure behavior change acute chronic back pain, but mechanisms are surprisingly poorly understood link between structure is tenuous. Although have potential to unify...
Abstract Purpose Proprioceptive deficits are common in low back pain. The multifidus muscle undergoes substantial structural change after injury, but whether spindles affected is unclear. This study investigated of the changed by intervertebral disc (IVD) degeneration a large animal model. Methods IVD was induced partial thickness annulus fibrosus lesion to L3-4 nine sheep. Multifidus tissue at L4 harvested six months lesion, and from age-/sex-matched naïve control animals. Muscle were...
To investigate the role of heparan sulfate (HS) proteoglycan perlecan (HSPG-2) in regulating fibroblast growth factor (FGF) activity, bone and joint growth, onset progression posttraumatic osteoarthritis (OA) a mouse gene-knockout model.Maturational changes were evaluated histologically knees 3-, 6-, 12-week-old wild-type (WT) mice Hspg2(Δ3-/Δ3-) (Hspg2 lacking domain 1 HS, generated by ablation exon 3 perlecan). Cartilage damage, subchondral sclerosis, osteophytosis, synovial inflammation...
Study Design. In-vivo ovine model of intervertebral disc degeneration (IVD) to evaluate treatment with stem cells. Objective. To determine if cells delivered the nucleus pulposus (NP) or annulus fibrosus (AF) degenerated lumbar IVDs leads improved indices health. Summary Background Data. Previous studies assessing efficacy cell injections into have reported positive findings. However, been limited small animals, targeting solely NP, short term follow-up. Methods. Mesenchymal precursor (MSC)...
Abstract Background Synovitis is implicated in the severity and progression of pain structural pathology osteoarthritis (OA). Increases inflammatory or immune cell subpopulations including macrophages lymphocytes have been reported OA synovium, but how particular influence symptomatic disease unclear. Two therapies, hyaluronan (HA) mesenchymal stem cells (MSCs), demonstrated efficacy some clinical settings: HA acting as device to improve joint function provide relief, while MSCs may...
An investigation of mechanical destabilization the lumbar ovine intervertebral disc (IVD) inducing IVD degeneration (IVDD) as determined by multiparameter outcome measures (magnetic resonance imaging [MRI], composition, biomechanical testing, gene profiling, immunohistochemistry, and immunoblotting).To assess effect on matrix protein metalloproteinase expression to investigate pathophysiological mechanisms IVDD.Several earlier studies have used annular transection induce IVDD in sheep, but...
The purpose of this study was to develop a quantitative histopathological scoring scheme evaluate disc degeneration and regeneration using an ovine annular lesion model experimental degeneration. Toluidine blue Haematoxylin Eosin (H&E) staining were used cellular morphology: (i) structure/lesion morphology; (ii) proteoglycan depletion; (iii) (iv) blood vessel in-growth; (v) cell influx into lesion; (vi) cystic degeneration/chondroid metaplasia. Three groups examined: 5 × mm 6 20 plus...
The aim of this study was to immunolocalise type VI collagen and perlecan determine their interactive properties in the intervertebral disc (IVD). Confocal laser scanning microscopy co-localised with as pericellular components IVD cells translamellar cross-bridges ovine murine IVDs. These were significantly less abundant heparin sulphate deficient Hspg2 exon 3 null mouse than wild type. This association elastic provides clues its roles conveying recoil annular tissues. Perlecan highly...
Intervertebral disc degeneration/low back pain is the number one global musculoskeletal condition in terms of disability and socioeconomic impact.Multipotent mesenchymal stem cells (MSCs) were cultured micromass pellets ± FGF-2 or -18 up to 41 days, matrix components immunolocalized gene expression monitored by quantitative-reverse transcription PCR.Chondrogenesis occurred earlier FGF-18 than cultures. Lower COL2A1, COL10A1 ACAN day indicated a downregulation chondrocyte hypertrophy. MEF2c,...
The role of hyaluronan (HA) oligosaccharides in disc cell-mediated matrix metalloproteinase (MMP) and anabolic gene expression vitro annular repair vivo were examined. Monolayer alginate bead cultures ovine intervertebral cells stimulated with 10–12 mer (HA-oligos). Annulus fibrosus (AF) monolayers poorly responsive to the HA-oligos, proMMP-2 levels marginally elevated MMP-9 unaffected. ProMMP-2 displayed a strong dose-dependent increase nucleus pulposus (NP) monolayers. In AF cultures,...
Forty percent of low back pain cases are due to intervertebral disc degeneration (IVDD), with mesenchymal stem cells (MSCs) a reported treatment. We utilized an ovine IVDD model and intradiscal heterologous MSCs determine therapeutic efficacy at different stages IVDD.Three nonoperated control (NOC) sheep were used for MSC isolation. In 36 sheep, 6 × 20 mm annular lesions made three spinal levels using customized blades/scalpel handles, was allowed develop 4 weeks in the Early (EA) late Acute...
Study Design. Longitudinal case-control animal model. Objective. To investigate effects of mesenchymal stem cell (MSC) treatment on multifidus muscle remodeling after intervertebral disc (IVD) lesion. Summary Background Data. Lesion and degeneration IVDs cause structural the muscle. Proinflammatory cytokines are thought to contribute. MSC restores IVD health lesion but its surrounding tissues remains unknown. Using an model degeneration, we assessed cytokine expression within Methods. An...
Background: Cartilage regeneration requires a balance of anabolic and catabolic processes. Aim: To examine the susceptibility fibromodulin (FMOD) lumican (LUM) to degradation by MMP-13, ADAMTS-4 ADAMTS-5, three major degradative proteinases in articular cartilage, cartilage development osteoarthritis (OA). Methods: Immunolocalization FMOD LUM fetal foot adult knee cartilages using an matrix metalloprotease (MMP)-13 neoepitope antibody (TsYG11) C-terminal anti-FMOD (PR184) anti-LUM (PR353)...
Objective The prevalence of comorbid chronic kidney disease (CKD) and osteoarthritis (OA) is increasing globally. While sharing common risk factors, the mechanism consequences concurrent CKD-OA are unclear. aims study were to develop a preclinical model, investigate disease-modifying interactions. Methods Seventy (70) male 8–10 week-old C57BL/6 mice subjected 5/6 nephrectomy (5/6Nx)±destabilisation medial meniscus (DMM) or sham surgery. OA pathology CKD assessed 12 weeks postinduction by...
ObjectiveHistological scoring remains the gold-standard for quantifying post-traumatic osteoarthritis (ptOA) in animal models, allowing concurrent evaluation of numerous joint tissues. Available systems require multiple sections/joint making analysis laborious and expensive. We investigated if a single section allowed equivalent quantitation pathology different tissues disease stages, three ptOA models.MethodMale 10-12-week-old C57BL/6 mice underwent surgical medial-meniscal-destabilization,...
Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases, affecting patients suffering from pain and physical limitations. Recent evidence indicates a potential inflammatory component disease, with both T-cells monocytes/macrophages potentially associated pathogenesis OA. Further studies postulated an important role for subsets cell lineages, such as Th1, Th2, Th17, T-regulatory lymphocytes, M1, M2, synovium-tissue-resident macrophages. However, interaction between local...
The most common treatment for osteoarthritis is daily oral administration of a nonsteroidal anti-inflammatory drug such as diclofenac. This dosage regime often associated with severe side effects. In this study, we explored the potential utilizing high molecular weight cross-linked polyurethane polymer covalently linked to diclofenac (C-DCF-PU) intra-articular administration. We aim exploit advantages local delivery by developing an implant improved efficacy and reduced was synthesized from...