Margaret Mary Smith

Royal North Shore Hospital · Department of Orthopaedics

Pentosan polysulfate (PPS), a small semi-synthetic highly sulfated heparan sulfate (HS)-like molecule, shares many of the interactive properties of HS. The aim of this review was to outline the potential of PPS as an interventional therapeutic protective agent in physiological processes affecting pathological tissues. PPS is a multifunctional molec...

The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bio...

This narrative review highlights the complexities of the gut microbiome and health-promoting properties of prebiotic xylans metabolized by the gut microbiome. In animal husbandry, prebiotic xylans aid in the maintenance of a healthy gut microbiome. This prevents the colonization of the gut by pathogenic organisms obviating the need for dietary anti...

This review highlights the attributes of pentosan polysulphate (PPS) in the promotion of intervertebral disc (IVD) repair processes. PPS has been classified as a disease modifying osteoarthritic drug (DMOAD) and many studies have demonstrated its positive attributes in the countering of degenerative changes occurring in cartilaginous tissues during...

Résumé Introduction La rupture dégénérative de la coiffe des rotateurs est une pathologie fréquente et multifactorielle. Le rôle de la morphologie osseuse de la grande tubérosité et de l’acromion latéral a été validé et peut être mesuré avec deux marqueurs radiographiques sur des clichés de face : le Greater Tuberosity Angle [Angle du Tubercule Ma...

Objective A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is a key enzyme in degradation of cartilage in osteoarthritis (OA). We report the pharmacological characterization of GLPG1972/S201086, a new, potent and selective small-molecule ADAMTS5 inhibitor. Methods Potency and selectivity of GLPG1972/S201086 for ADAMTS5 we...

Background: Degenerative rotator cuff tear is a frequent and multifactorial pathology. The role of bone morphology of the greater tuberosity and lateral acromion has been validated, and can be measured with two plain radiographic markers on true anteroposterior views: the greater tuberosity angle (GTA) and the critical shoulder angle (CSA). However...

Objective To determine whether osteoarthritis (OA) pain characteristics and mechanistic pathways in pre-clinical models are phenotype-specific. Design Male 11-week-old C57BL6 mice had unilateral medial-meniscal-destabilization (DMM) or antigen-induced-arthritis (AIA), versus sham-surgery/immunised-controls (Sham/Im-CT). Pain-behaviour (allodynia,...

Background Hematoma formation and blood transfusions are commonly reported complications after shoulder arthroplasty. Tranexamic acid (TXA) has been widely used in hip and knee arthroplasty to decrease perioperative blood loss. The role of TXA is still being established in shoulder arthroplasty. Materials and Methods We conducted a double-blinded...

Category Bunion Introduction/Purpose Little is known about the long-term results of percutaneous hallux valgus correction, particularly the recurrence rate and factors leading to recurrence. Methods We retrospectively reviewed a single surgeon consecutive series of percutaneous chevron and akin osteotomies (PECA) performed between 2012-14 on 127...

Background: Extra-articular fluid extravasation is a known complication during shoulder arthroscopy. The risk and amount of extravasation to a large degree is dependent on the fluid pressure delivered to the surgical site. Accurate measurement, knowledge, and control of the pressure delivered is thus important to surgeons, anesthetists, and the pat...

Background Extra-articular fluid extravasation is a known complication during shoulder arthroscopy. The risk and amount of extravasation to a large degree is dependent on the fluid pressure delivered to the surgical site. Accurate measurement, knowledge and control of the pressure delivered is thus important to surgeons, anesthetists and the patien...

Objective To determine if osteoarthritis (OA) progression and joint tissue-pathology associations link specific animal models to different human OA phenotypes. Design Male 11-week-old C57BL6 mice had unilateral medial-meniscal-destabilization (DMM) or antigen-induced-arthritis (AIA). Joint tissue histopathology was scored day-3 to week-16. Tissue-...

Background: Synovitis is implicated in the severity and progression of pain and structural pathology of osteoarthritis (OA). Increases in inflammatory or immune cell subpopulations including macrophages and lymphocytes have been reported in OA synovium, but how the particular subpopulations influence symptomatic or structural OA disease progressio...

Objectives: Identification of osteoarthritis(OA)-specific synovial inflammatory pathways, and when in the clinical course they are active, is critical for their utility as therapeutic targets. We directly compared the mononuclear inflammatory/immune-cell responses following joint injury that does and does-not lead to OA, to define bona-fide OA-asso...

Purpose: To evaluate the viscoelastic properties of 4 commercially available cord-like sutures and 2 commercially available suture tapes when subjected to physiological loads, as well as to compare them with each other and to identify the clinically most desirable combination of suture material properties. Methods: Six suture materials (Ethibond...

Tendons with different in vivo functions are known to have different baseline biomechanics, biochemistry and ultrastructure, and these can be affected by changes in loading. However it is not know whether different tendon types respond in the same, or different ways, to changes in loading. This study performed in vitro un-loading (stress deprivatio...

Following injury to a tendon little is known about potential for pathology to develop in other regional tendons from overloading or altered function. The aim of this study was to investigate the gene expression and histopathological changes that occur 1) within the deep digital flexor tendon (DDFT) after injury to the superficial digital flexor ten...

Comparison of histology scores within the SDFT between non-operated control (NOC) and transected extensor tendons (TxEXT). Significance was set at P<0.05 (bold). MWU = Mann-Whitney U analysis; NOC = non-operated control; TxEXT = completely transected extensor tendons. (DOCX)

Histology scores and descriptions. Histology scoring parameters are shown. Total histopathology score was calculated from the sum of all scores except proteoglycan content. A higher score indicated a tendon with a more pathological appearance. (DOCX)

Analysed genes and relevant primers. Analysed genes (with standard abbreviations as used in the text), primer sequences, annealing temperatures and product sizes are shown. (DOCX)

Dataset with raw data for all gene expression and histology analyses. (XLSX)

Background The aim of our study was to identify the demographics and complications in elderly cervical spine injuries and predictive factors for surgery, complications and mortality. We hypothesized younger healthier patients were more likely to undergo surgical intervention. Methods A retrospective review of 225 consecutive patients aged 65 years...

Purpose: Summarise available evidence comparing the cellular, biochemical, structural and biomechanical properties, and the changes that occur in these parameters in response to stimuli, in differentially loaded tendons across different stages of life. Methods: The PubMed database was searched for literature pertaining to differences between ten...

The aim of this study was to determine the role of the perlecan (Hspg2) heparan sulphate (HS) side chains on cell and matrix homeostasis in tail and Achilles tendons in 3 and 12 week old Hspg2 exon 3 null HS deficient ( Hspg2Δ3 − ∕Δ3 − ) and C57 BL/6 Wild Type (WT) mice. Perlecan has important cell regulatory and matrix organizational properties th...

Genotyping of WT and Hspg2 exon 3 null murine genomic DNA and Western blotting of perlecan isolated from the two mouse genotypes Specific regions of the mouse perlecan gene were amplified by PCR using genotyping primers recognising intron 2 of mouse Hspg2 (GTA GGG ACA CTT GTC ATC CT), exon 3 (CTG CCA AGG CCA TCT GCA AG) and Hspg2Δ3−∕Δ3− (AGG AGT AG...

Raw RT PCR, biomechanics, mouse weights, compositional data for wild type and perlecan exon 3 null mouse tail and Achilles tendon

Background: Most glenoid version measurement methods have been validated on 3-dimensionally corrected axial computed tomography (CT) slices at the mid glenoid. Variability of the vault according to slice height and angulation has not yet been studied and is crucial for proper surgical implant positioning. The aim of this study was to analyze the v...

Background: The implication of scapular morphology in rotator cuff tears has been extensively studied. However, the role of the greater tuberosity (GT) should be of equal importance. The aim of this study was to propose a new radiographic marker, the GT angle (GTA), which measures the position of the GT in relation to the center of rotation of the...

The aim of this study was to determine the regulatory role of the perlecan HS side chains on cell and matrix homeostasis in tail and Achilles tendons in 3 and 12 week old Hspg2 exon 3 null HS deficient ( Hspg2 ∆3-/∆3- ) and C57 BL/6 Wild Type (WT) mice. Tendons were biomechanically tested (ultimate tensile stress [UTS], tensile modulus [TM]) and gl...

The aim of this study was to determine the regulatory role of the perlecan HS side chains on cell and matrix homeostasis in tail and Achilles tendons in 3 and 12 week old Hspg2 exon 3 null HS deficient ( Hspg2 ∆3-/∆3- ) and C57 BL/6 Wild Type (WT) mice. Tendons were biomechanically tested (ultimate tensile stress [UTS], tensile modulus [TM]) and gl...

Introduction: The role of temporomandibular joint (TMJ) surgery is not well defined due to a lack of quality randomized controlled clinical trials, comparing different TMJ surgical treatments with medical and placebo interventions. The temporomandibular joint interposal study (TEMPOJIMS) is a rigorous preclinical trial divided in 2 phases. In phas...

Realignment therapies, including knee braces, foot orthoses and shoes are prescribed to patients with medial knee osteoarthritis (OA) with the goal of unloading the medial tibiofemoral (TF) compartment. It is uncertain whether realignment therapies have different effects in those with knee malalignment. We studied whether the efficacy of realignmen...

Flexor tendinopathy is a common problem affecting humans and animals. Tendon healing is poorly understood and the outcomes of conservative and surgical management are often suboptimal. While often considered a localized injury, recent evidence indicates that in the short term, tendinopathic changes are distributed widely throughout the tendon, remo...

Histology scores and descriptions. Histology scoring parameters are shown. Slides were scored by three separate observers and a mean score calculated. The total histopathology score was calculated by adding all scores (except the proteoglycan score). A higher score indicated a tendon with a more pathological appearance. (DOCX)

Histology scoring odds ratios for spatiotemporal covariates with and without surgery by mixed ordinal logistic regression. Ratios are presented for non-operated controls (contralateral tendons and sham operated) and for both operated and non-operated tendons. CI = confidence intervals; 5% significance level is P<0.025 after Benjamini-Hochberg corre...

Analysed genes and relevant primers. Analysed genes (with standard abbreviations as used in the text), gene sequence accession numbers, primer sequences, annealing temperatures and product sizes are shown. (DOCX)

Dataset with raw data for all gene expression, biomechanics and histology analyses. (XLSX)

The purpose of this study was to develop a quantitative histopathological scoring scheme to evaluate disc degeneration and regeneration using an ovine annular lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc structure/lesion morphology; (ii)...

Background: Minimally invasive surgery is being used increasingly, including for hallux valgus surgery. Despite the growing interest in minimally invasive procedures, there have been few publications on percutaneous chevron/akin (PECA) procedures, and no studies have been published comparing PECA to open scarf/akin osteotomies (SA). Methods: Thi...

Objective To review the factors in experimental design that contribute to poor translation of pre-clinical research to therapies for patients with osteoarthritis (OA) and how this might be improved. Methods Narrative review of the literature, and evaluation of the different stages of design conduct and analysis of studies using animal models of OA...

Background: Propionibacterium acnes is a common pathogen identified in postoperative shoulder infection. It has been shown to be present in culture specimens during primary shoulder arthroplasty; however, recent work has suggested that it is most likely to be a contaminant. Our aim was to identify the potential sources of contamination in shoulder...

The role of hyaluronan (HA) oligosaccharides in disc cell mediated matrix metalloproteinase (MMP) and anabolic gene expression in-vitro and annular repair in-vivo were examined in this study. Monolayer and alginate bead cultures of ovine intervertebral disc cells were stimulated with 10-12 mer hyaluronan oligosaccharides (HA-oligos). Annulus fibros...

Objective: The purpose of this study was to determine if serum microRNA (miRNA) signatures were biomarkers of early cartilage degeneration in preclinical mouse models of post-traumatic osteoarthritis and inflammatory arthritis. Methods: Cartilage degeneration was induced in 10-12 week old male C57BL6 mice by destabilization of the medial meniscu...

Both mechanical and structural properties of tendon change after injury however the causal relationship between these properties is presently unclear. This study aimed to determine the extent of biomechanical change in post-injury tendon pathology and whether the sulphated glycosaminoglycans (glycosaminoglycans) present are a causal factor in these...

Objective: To investigate the role of perlecan heparan sulfate (HS) in regulating fibroblast growth factor (FGF) activity, bone and joint growth and the onset/progression of post-traumatic osteoarthritis (ptOA). Methods: Maturational changes in 3, 6 and 12 week-old wildtype (WT) and perlecan exon-3-null (Hspg2 lacking domain-1 HS) mouse knees we...

It is not known how extensively a localised flexor tendon injury affects the entire tendon. This study examined the extent of and relationship between histopathologic and gene expression changes in equine superficial digital flexor tendon after a surgical injury. One forelimb tendon was hemi-transected in six horses, and in three other horses, one...

Study design: Retrospective case series. Objective: To test validity of subaxial injury classification (SLIC) treatment recommendations. Summary of background data: Although SLIC has been tested for reliability, external studies that test the validity of its treatment recommendations are lacking. Methods: The SLIC score was determined by rev...

Objective: To explore the involvement of protease-activated receptor 1 (PAR-1) and PAR-2 in the pathologic processes of osteoarthritis (OA) and to identify the cells/tissues primarily affected by ablation of PAR-1 or PAR-2 in mice. Methods: OA was induced in the joints of wild-type (WT), PAR-1(+/+) , PAR-1(-/-) , and PAR-2(-/-) mice by destabili...

Introduction Rotator cuff healing after injury and/or repair is often compromised by excessive fibrosis both at the lesion site and in the surrounding tendon, particularly in patients with diabetes. Diabetic and hyperglycaemic patients have a higher incidence of tendinopathy than healthy populations. Proposed explanations, including a direct effect...

Objective: Levels of activated protein C (APC) are elevated in the synovial fluid of patients with osteoarthritis (OA), and increased APC levels are correlated with the levels of active matrix metalloproteinase 2 (MMP-2). This study sought to investigate whether APC is a relevant protein for activation of MMPs in the degradation of human OA cartil...

Purpose: Sclerostin (SOST) and dikkopf-1 (DKK1) are secreted proteins that inhibit Wnt signaling. Increased Wnt-β-catenin activity is implicated in cartilage degradation in osteoarthritis (OA) at the same time driving increased bone formation (subchondral thickening osteophytes) that typifies OA. This suggests that increasing SOST/DKK1 may be prote...

Significance: Proteoglycans have a distinct spatial localization in normal skin and are essential for the correct structural development, organization, hydration, and functional properties of this tissue. The extracellular matrix (ECM) is no longer considered to be just an inert supportive material but is a source of directive, spatial and temporal...

Intra-articular hyaluronan (HA) injection provides symptomatic benefit in the treatment of osteoarthritis (OA). Previously we found superior beneficial effects in a large animal OA model of a hexadecylamide - derivative compared with unmodified HA of the same initial molecular weight. The current study sought to define possible molecular mechanisms...

Composite agarose (1.2 %) polyacrylamide (0.6 %) gel electrophoresis was used to separate discrete populations of native aggrecan and perlecan in newborn to 10 year old ovine intervertebral discs (IVDs). Semi-dry immunoblotting using core-protein and glycosaminoglycan (GAG) side chain specific monoclonal antibodies in combination with chondroitin A...

Tendon tears are common in both the ageing and sporting communities. Treatments that restore normal structure and function are lacking despite increasing knowledge of the inflammatory and matrix changes that occur in the tissue after a stress-induced injury. Increased cellularity, disruption of collagen fibre alignment and excessive accumulation of...

One of the hallmarks of developing tendinopathy after injury is the accumulation of toluidine-blue-positive sulfated glycosaminoglycan, attributed to increased expression and synthesis of the large proteoglycans (PGs) aggrecan and versican. Indeed, there is evidence that, in many instances, these molecules are already chronically present in the ten...

Activated protein C (APC) promotes angiogenesis and reepithelialisation and accelerates healing of diabetic ulcers. The aim of this study was to determine the relationship between the incidence of lower leg ulcers and plasma levels of APC's precursor, protein C (PC), in diabetic patients. Patients with diabetes who had a lower leg ulcer(s) for >6 m...

Perlecan is a widely distributed, heparan sulphate proteoglycan with roles in the sequestration of FGFs, PDGF, VEGF through which it promotes cell proliferation and matrix production. Perlecan also stabilises extracellular matrices through interaction with a diverse range of matrix components. This study examined the distribution of perlecan in an...

Objective(s): Meniscectomy (MX) of sheep induces a well-established animal model of human osteoarthritis (OA). This study compared the clinical (lameness) and pathological outcomes of unilateral, complete medial MX vs two less traumatic and more easily performed meniscal destabilisation procedures. Methods: Four-year old wethers (n = 6/group) un...

An investigation of mechanical destabilization of the lumbar ovine intervertebral disc (IVD) inducing IVD degeneration (IVDD) as determined by multiparameter outcome measures (magnetic resonance imaging [MRI], IVD composition, biomechanical testing, gene profiling, immunohistochemistry, and immunoblotting). To assess the effect of IVD mechanical de...

To determine the mechanisms of meniscal degeneration and whether this varied zonally and from articular cartilage. Normal ovine menisci were dissected into inner and outer zones and along with cartilage cultured ±IL-1α and TNFα. Glycosaminoglycan (GAG) and collagen release, and gene expression were quantified. Aggrecan proteolysis was analysed by W...

Rheumatoid arthritis affecting the shoulder is typically associated with rotator cuff compromise and can also result in severe glenoid erosion. Since reverse shoulder arthroplasty is capable of addressing both rotator cuff disorders and glenoid bone deficiencies, our aim was to evaluate the outcome of reverse shoulder arthroplasty in patients with...

We have colocalized elastin and fibrillin-1 with perlecan in extracellular matrix of tensional and weight-bearing connective tissues. Elastin and fibrillin-1 were identified as prominent components of paraspinal blood vessels, and posterior longitudinal ligament in the human fetal spine and outer annulus fibrosus of the fetal intervertebral disc. W...

To investigate the regulation of sclerostin (SOST) in osteoarthritis (OA) and its potential effects on articular cartilage degradation. SOST and other Wnt-β-catenin components were immuno-localised in osteochondral sections of surgically-induced OA in knees of sheep and mice, and human OA samples obtained at arthroplasty. Regulation of SOST mRNA an...