The Interfascicular Matrix of Energy Storing Tendons Houses Heterogenous Cell Populations Disproportionately Affected by Aging.

Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to injury, with incidence increasing with aging, peaking in the 5th decade of life in the human Achilles tendon. The interfascicular matrix (IFM), which binds tendon fascicles, plays a key role in energy storing tendon mechanics, and aging alterations to the IFM negatively impact tendon function. While the mechanical role of the IFM in tendon function is well-established, the biological role of IFM-resident cell populations remains to be elucidated. Therefore, the aim of this study was to identify IFM-resident cell populations and establish how these populations are affected by aging. Cells from young and old SDFTs were subjected to single cell RNA-sequencing, and immunolabelling for markers of each resulting population used to localise cell clusters. Eleven cell clusters were identified, including tenocytes, endothelial cells, mural cells, and immune cells. One tenocyte cluster localised to the fascicular matrix, whereas nine clusters localised to the IFM. Interfascicular tenocytes and mural cells were preferentially affected by aging, with differential expression of genes related to senescence, dysregulated proteostasis and inflammation. This is the first study to establish heterogeneity in IFM cell populations, and to identify age-related alterations specific to IFM-localised cells.

MicroRNA Signatures in Cartilage Ageing and Osteoarthritis.

Osteoarthritis is the most common degenerative joint disorder. MicroRNAs are gene expression regulators that act post-transcriptionally to control tissue homeostasis. Microarray analysis was undertaken in osteoarthritic intact, lesioned and young intact cartilage. Principal component analysis showed that young intact cartilage samples were clustered together; osteoarthritic samples had a wider distribution; and osteoarthritic intact samples were separated into two subgroups, osteoarthritic-Intact-1 and osteoarthritic-Intact-2. We identified 318 differentially expressed microRNAs between young intact and osteoarthritic lesioned cartilage, 477 between young intact and osteoarthritic-Intact-1 cartilage and 332 between young intact and osteoarthritic-Intact-2 cartilage samples. For a selected list of differentially expressed microRNAs, results were verified in additional cartilage samples using qPCR. Of the validated DE microRNAs, four-miR-107, miR-143-3p, miR-361-5p and miR-379-5p-were selected for further experiments in human primary chondrocytes treated with IL-1ß. Expression of these microRNAs decreased in human primary chondrocytes treated with IL-1ß. For miR-107 and miR-143-3p, gain- and loss-of-function approaches were undertaken and associated target genes and molecular pathways were investigated using qPCR and mass spectrometry proteomics. Analyses showed that WNT4 and IHH, predicted targets of miR-107, had increased expression in osteoarthritic cartilage compared to young intact cartilage and in primary chondrocytes treated with miR-107 inhibitor, and decreased expression in primary chondrocytes treated with miR-107 mimic, suggesting a role of miR-107 in chondrocyte survival and proliferation. In addition, we identified an association between miR-143-3p and EIF2 signalling and cell survival. Our work supports the role of miR-107 and miR-143-3p in important chondrocyte mechanisms regulating proliferation, hypertrophy and protein translation.

Collagen (I) homotrimer potentiates the osteogenesis imperfecta (oim) mutant allele and reduces survival in male mice.

The osteogenesis imperfecta murine (oim) model with solely homotrimeric (α1)3 type I collagen, owing to a dysfunctional α2(I) collagen chain, has a brittle bone phenotype, implying that the (α1)2(α2)1 heterotrimer is required for physiological bone function. Here, we comprehensively show, for the first time, that mice lacking the α2(I) chain do not have impaired bone biomechanical or structural properties, unlike oim homozygous mice. However, Mendelian inheritance was affected in male mice of both lines, and male mice null for the α2(I) chain exhibited age-related loss of condition. Compound heterozygotes were generated to test whether gene dosage was responsible for the less-severe phenotype of oim heterozygotes, after allelic discrimination showed that the oim mutant allele was not downregulated in heterozygotes. Compound heterozygotes had impaired bone structural properties compared to those of oim heterozygotes, albeit to a lesser extent than those of oim homozygotes. Hence, the presence of heterotrimeric type I collagen in oim heterozygotes alleviates the effect of the oim mutant allele, but a genetic interaction between homotrimeric type I collagen and the oim mutant allele leads to bone fragility.

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 histological and gene expression analysis. Relations between POD grade, cartilage histological score, and gene expression levels were examined using one-way analysis of variance or Kruskal-Wallis test and Spearman's correlation coefficient with corrections for multiple comparisons. Cartilage histological score increased in joints with POD grade 1 (p = 0.002) and 2 or 3 (p < 0.001) compared to 0. At grade 1, expression of COL1A1, COL2A1, and MMP1 increased and BGN decreased in subchondral bone while expression of BGN and ACAN decreased in cartilage. These changes further progressed at grades 2 and 3. POD grades 2 and 3 were associated with decreased expression of osteoclast inhibitor OPG and increased markers of cartilage degeneration (MMP13, COL1A1). Expression of the vascular endothelial growth factor decreased with POD grade and negatively correlated with cartilage histological score. Synovium showed no histological or transcriptomic changes related to pathology grade. Cartilage degeneration in POD is likely to be secondary to remodeling of the subchondral bone. Limited activation of proinflammatory and catabolic genes and moderate synovial pathology suggests distinct molecular phenotype of POD compared with OA.

Antimicrobial resistance in clinical bacterial isolates from horses in the UK.

BACKGROUND: Surveillance of antimicrobial resistance (AMR) in horses is important to aid empirical treatment decisions and highlight emerging AMR threats. OBJECTIVE: To describe the AMR patterns of common groups of bacteria from clinical submissions from horses in the UK during 2018, and to determine how this varies by sample site and type of submitting veterinary practice. STUDY DESIGN: Prospective observational study. METHODS: All data on bacterial culture and subsequent antimicrobial susceptibility testing (AST) collected in 2018 from six large equine diagnostic laboratories were included. Resistance patterns were analysed including resistance to 1 or 2 antimicrobial classes, multidrug resistance (MDR), extensively drug resistant (XDR), resistance to highest priority critically important antimicrobials and isolates where there was no readily available treatment for adult horses in the UK. Submitting practices were classified according to whether they treated referral cases or not (first opinion). Comparisons between proportions and resistance for each bacterial group and sample site was performed using Chi-squared (or Fisher's exact test). RESULTS: A total of 6,018 bacterial isolates from 4,038 diagnostic submissions were included from respiratory (n = 1555), urogenital (n = 1,010), skin/hair/wound/abscess (n = 753), surgical site infection (SSI) /catheter-related-infection (CRI) /orthopaedic infections (n = 347) and unknown/'other' submissions (n = 373). There were 2,711 Gram-negative isolates and 3,307 Gram-positive isolates. Prevalence of MDR for E. coli was 31.7%, Staphylococcus spp. 25.3% and > 25% for the majority of bacterial isolates from SSI/CRI/orthopaedic submissions. For Enterococcus spp. there was no readily available treatment for adult horses in the UK in 30.2% of positive submissions. MDR was significantly higher from referral hospital than first opinion submissions for the majority of pathogens (except Actinobacillus spp. and Pasteurella spp. and ß-haemolytic Streptococcus spp.). MAIN LIMITATIONS: Since culture and susceptibility results are not systematic analyses based on harmonised methods, selection bias could impact the findings. CONCLUSIONS: Ongoing surveillance is essential to understand emerging patterns of resistance. MDR is high in SSI/CRI/orthopaedic infections, which is important for hospital biosecurity and guiding treatment decisions. Harmonisation of diagnostic procedures and interpretation of results amongst veterinary laboratories will improve AMR surveillance and data comparison among laboratories.

Equine flexor tendon imaging part 2: Current status and future directions in advanced diagnostic imaging, with focus on the deep digital flexor tendon.

Flexor tendon injuries are a common cause of lameness and early retirement in equine athletes. While ultrasonography is most frequently utilised, advanced diagnostic imaging modalities are becoming more widely available for detection and monitoring of flexor tendon lesions. Part two of this literature review details current experience with low- and high-field magnetic resonance imaging (MRI) and computed tomography (CT) for the diagnosis of equine flexor tendinopathy with a focus on the deep digital flexor tendon. Implications of the 'magic angle' artefact as well as injection techniques and the use of contrast media are discussed. Future developments in tendon imaging aim to gain enhanced structural information about the tendon architecture with the prospect to prevent injury. Techniques as described for the assessment of the human Achilles tendon including ultra-high field MRI and positron emission tomography are highlighted.

Equine flexor tendon imaging part 1: Recent developments in ultrasonography, with focus on the superficial digital flexor tendon.

Flexor tendon injuries are a major cause of lameness in performance horses and have considerable impact on equine welfare and the wider horse industry. Ageing and repetitive strain frequently cause varying degrees of tendon micro-damage prior to the recognition of clinical tendinopathy. Whilst B-mode ultrasonography is most commonly utilised for detection and monitoring of tendon lesions at the metacarpal/metatarsal level, the emphasis of recent research has focused on the identification of subclinical tendon damage in order to prevent further tendon injury and improve outcomes. The introduction of elastography, acoustoelastography and ultrasound tissue characterisation in the field of equine orthopaedics shows promising results and might find wider use in equine practice as clinical development continues. Based on the substantial number of research studies on tendon imaging published over the past decade this literature review aims to examine the currently used ultrasonographic imaging techniques and their limitations, and to introduce and critically appraise new modalities that could potentially change the clinical approach to equine flexor tendon imaging.

Structure-function specialisation of the interfascicular matrix in the human achilles tendon.

Tendon consists of highly aligned collagen-rich fascicles surrounded by interfascicular matrix (IFM). Some tendons act as energy stores to improve locomotion efficiency, but such tendons commonly obtain debilitating injuries. In equine tendons, energy storing is achieved primarily through specialisation of the IFM. However, no studies have investigated IFM structure-function specialisation in human tendons. Here, we compare the human positional anterior tibial tendon and energy storing Achilles tendons, testing the hypothesis that the Achilles tendon IFM has specialised composition and mechanical properties, which are lost with ageing. Data demonstrate IFM specialisation in the energy storing Achilles, with greater elasticity and fatigue resistance than in the positional anterior tibial tendon. With ageing, alterations occur predominantly to the proteome of the Achilles IFM, which are likely responsible for the observed trends towards decreased fatigue resistance. Knowledge of these key energy storing specialisations and their changes with ageing offers crucial insight towards developing treatments for tendinopathy. STATEMENT OF SIGNIFICANCE: Developing effective therapeutics or preventative measures for tendon injury necessitates the understanding of healthy tendon function and mechanics. By establishing structure-function relationships in human tendon and determining how these are affected by ageing, potential targets for therapeutics can be identified. In this study, we have used a combination of mechanical testing, immunolabelling and proteomics analysis to study structure-function specialisations in human tendon. We demonstrate that the interfascicular matrix is specialised for energy storing in the Achilles tendon, and that its proteome is altered with ageing, which is likely responsible for the observed trends towards decreased fatigue resistance. Knowledge of these key energy storing specialisations and their changes with ageing offers crucial insight towards developing treatments and preventative approaches for tendinopathy.

Intrafascicular chondroid-like bodies in the ageing equine superficial digital flexor tendon comprise glycosaminoglycans and type II collagen.

The superficial digital flexor tendon (SDFT) is considered functionally equivalent to the human Achilles tendon. Circular chondroid depositions scattered amongst the fascicles of the equine SDFT are rarely reported. The purpose of this study was the detailed characterization of intrafascicular chondroid-like bodies (ICBs) in the equine SDFT, and the assessment of the effect of ageing on the presence and distribution of these structures. Ultrahigh field magnetic resonance imaging (9.4T) series of SDFT samples of young (1-9 years) and aged (17-25 years) horses were obtained, and three-dimensional reconstruction of ICBs was performed. Morphological evaluation of the ICBs included histology, immunohistochemistry and transmission electron microscopy. The number, size, and position of ICBs was determined and compared between age groups. There was a significant difference (p = .008) in the ICB count between young and old horses with ICBs present in varying number (13-467; median = 47, mean = 132.6), size and distribution in the SDFT of aged horses only. There were significantly more ICBs in the tendon periphery when compared with the tendon core region (p = .010). Histological characterization identified distinctive cells associated with increased glycosaminoglycan and type II collagen extracellular matrix content. Ageing and repetitive strain frequently cause tendon micro-damage before the development of clinical tendinopathy. Documentation of the presence and distribution of ICBs is a first step towards improving our understanding of the impact of these structures on the viscoelastic properties, and ultimately their effect on the risk of age-related tendinopathy in energy-storing tendons.

Mouse microRNA signatures in joint ageing and post-traumatic osteoarthritis.

OBJECTIVE: This study investigated mice serum and joint microRNA expression profiles in ageing and osteoarthritis to elucidate the role of microRNAs in the development and progression of disease, and provide biomarkers for ageing and osteoarthritis. DESIGN: Whole joints and serum samples were collected from C57BL6/J male mice and subjected to small RNA sequencing. Groups used included; surgically-induced post-traumatic osteoarthritis, (DMM; 24 months-old); sham surgery (24 months-old); old mice (18 months-old); and young mice (8 months-old). Differentially expressed microRNAs between the four groups were identified and validated using real-time quantitative PCR. MicroRNA differential expression data was used for target prediction and pathway analysis. RESULTS: In joint tissues, miR-140-5p, miR-205-5p, miR-682, miR-208b-3p, miR-499-5p, miR-455-3p and miR-6238 were differentially expressed between young and old groups; miR-146a-5p, miR-3474, miR-615-3p and miR-151-5p were differentially expressed between DMM and Sham groups; and miR-652-3p, miR-23b-3p, miR-708-5p, miR-5099, miR-23a-3p, miR-214-3p, miR-6238 and miR-148-3p between the old and DMM groups. The number of differentially expressed microRNAs in serum was higher, some in common with joint tissues including miR-140-5p and miR-455-3p between young and old groups; and miR-23b-3p, miR-5099 and miR-6238 between old and DMM groups.We confirmed miR-140-5p, miR-499-5p and miR-455-3p expression to be decreased in old mouse joints compared to young, suggesting their potential use as biomarkers of joint ageing in mice. CONCLUSIONS: MiR-140-5p, miR-499-5p and miR-455-3p could be used as joint ageing biomarkers in mice. Further research into these specific molecules in human tissues is now warranted to check their potential suitability as human biomarkers of ageing.

Postnatal mechanical loading drives adaptation of tissues primarily through modulation of the non-collagenous matrix.

Mature connective tissues demonstrate highly specialised properties, remarkably adapted to meet their functional requirements. Tissue adaptation to environmental cues can occur throughout life and poor adaptation commonly results in injury. However, the temporal nature and drivers of functional adaptation remain undefined. Here, we explore functional adaptation and specialisation of mechanically loaded tissues using tendon; a simple aligned biological composite, in which the collagen (fascicle) and surrounding predominantly non-collagenous matrix (interfascicular matrix) can be interrogated independently. Using an equine model of late development, we report the first phase-specific analysis of biomechanical, structural, and compositional changes seen in functional adaptation, demonstrating adaptation occurs postnatally, following mechanical loading, and is almost exclusively localised to the non-collagenous interfascicular matrix. These novel data redefine adaptation in connective tissue, highlighting the fundamental importance of non-collagenous matrix and suggesting that regenerative medicine strategies should change focus from the fibrous to the non-collagenous matrix of tissue.

Epigenetic mechanisms in Tendon Ageing.

INTRODUCTION: Tendon is a composite material with a well-ordered hierarchical structure exhibiting viscoelastic properties designed to transfer force. It is recognized that the incidence of tendon injury increases with age, suggesting a deterioration in homeostatic mechanisms or reparative processes. This review summarizes epigenetic mechanisms identified in ageing healthy tendon. SOURCES OF DATA: We searched multiple databases to produce a systematic review on the role of epigenetic mechanisms in tendon ageing. AREAS OF AGREEMENT: Epigenetic mechanisms are important in predisposing ageing tendon to injury. AREAS OF CONTROVERSY: The relative importance of epigenetic mechanisms are unknown in terms of promoting healthy ageing. It is also unknown whether these changes represent protective mechanisms to function or predispose to pathology. GROWING POINT: Epigenetic markers in ageing tendon, which are under-researched including genome-wide chromatin accessibility, should be investigated. AREAS TIMELY FOR DEVELOPING RESEARCH: Metanalysis through integration of multiple datasets and platforms will enable a holistic understanding of the epigenome in ageing and its relevance to disease.

Ex Vivo Equine Cartilage Explant Osteoarthritis Model: A Metabolomics and Proteomics Study.

Osteoarthritis is an age-related degenerative musculoskeletal disease characterized by loss of articular cartilage, synovitis, and subchondral bone sclerosis. Osteoarthritis pathogenesis is yet to be fully elucidated with no osteoarthritis-specific biomarkers in clinical use. Ex vivo equine cartilage explants (n = 5) were incubated in tumor necrosis factor-α (TNF-α)/interleukin-1ß (IL-1ß)-supplemented culture media for 8 days, with the media removed and replaced at 2, 5, and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent one-dimensional (1D) 1H nuclear magnetic resonance metabolomic analysis, with media samples also undergoing mass spectrometry proteomic analysis. Within the cartilage, glucose and lysine were elevated following TNF-α/IL-1ß treatment, while adenosine, alanine, betaine, creatine, myo-inositol, and uridine decreased. Within the culture media, 4, 4, and 6 differentially abundant metabolites and 154, 138, and 72 differentially abundant proteins were identified at 1-2, 3-5, and 6-8 days, respectively, including reduced alanine and increased isoleucine, enolase 1, vimentin, and lamin A/C following treatment. Nine potential novel osteoarthritis neopeptides were elevated in the treated media. Implicated pathways were dominated by those involved in cellular movement. Our innovative study has provided insightful information on early osteoarthritis pathogenesis, enabling potential translation for clinical markers and possible new therapeutic targets.

Heterogeneity of proteome dynamics between connective tissue phases of adult tendon.

Maintenance of connective tissue integrity is fundamental to sustain function, requiring protein turnover to repair damaged tissue. However, connective tissue proteome dynamics remain largely undefined, as do differences in turnover rates of individual proteins in the collagen and glycoprotein phases of connective tissue extracellular matrix (ECM). Here, we investigate proteome dynamics in the collagen and glycoprotein phases of connective tissues by exploiting the spatially distinct fascicular (collagen-rich) and interfascicular (glycoprotein-rich) ECM phases of tendon. Using isotope labelling, mass spectrometry and bioinformatics, we calculate turnover rates of individual proteins within rat Achilles tendon and its ECM phases. Our results demonstrate complex proteome dynamics in tendon, with ~1000 fold differences in protein turnover rates, and overall faster protein turnover within the glycoprotein-rich interfascicular matrix compared to the collagen-rich fascicular matrix. These data provide insights into the complexity of proteome dynamics in tendon, likely required to maintain tissue homeostasis.

Muscles are anchored to bones through specialized tissues called tendons. Made of bundles of fibers (or fascicles) linked together by an 'interfascicular' matrix, healthy tendons are required for organisms to move properly. Yet, these structures are constantly exposed to damage: the interfascicular matrix, in particular, is highly susceptible to injury as it allows the fascicles to slide on each other. One way to avoid damage could be for the body to continually replace proteins in tendons before they become too impaired. However, the way proteins are renewed in these structures is currently not well understood ­ indeed, it has long been assumed that almost no protein turnover occurs in tendons. In particular, it is unknown whether proteins in the interfascicular matrix have a higher turn over than those in the fascicles. To investigate, Choi, Simpson et al. fed rats on water carrying a molecular label that becomes integrated into new proteins. Analysis of individual proteins from the rats' tendons showed great variation in protein turnover, with some replaced every few days and others only over several years. This suggests that protein turnover is actually an important part of tendon health. In particular, the results show that turnover is higher in the interfascicular matrix, where damage is expected to be more likely. Protein turnover also plays a part in conditions such as cancer, heart disease and kidney disease. Using approaches like the one developed by Choi, Simpson et al. could help to understand how individual proteins are renewed in a range of diseases, and how to design new treatments.

Optimization of Synovial Fluid Collection and Processing for NMR Metabolomics and LC-MS/MS Proteomics.

Synovial fluid (SF) is of great interest for the investigation of orthopedic pathologies, as it is in close proximity to various tissues that are primarily altered during these disease processes and can be collected using minimally invasive protocols. Multi-"omic" approaches are commonplace, although little consideration is often given for multiple analysis techniques at sample collection. Nuclear magnetic resonance (NMR) metabolomics and liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics are two complementary techniques particularly suited to the study of SF. However, currently there are no agreed upon standard protocols that are published for SF collection and processing for use with NMR metabolomic analysis. Furthermore, the large protein concentration dynamic range present within SF can mask the detection of lower abundance proteins in proteomics. While combinational ligand libraries (ProteoMiner columns) have been developed to reduce this dynamic range, their reproducibility when used in conjunction with SF, or on-bead protein digestion protocols, has yet to be investigated. Here we employ optimized protocols for the collection, processing, and storage of SF for NMR metabolite analysis and LC-MS/MS proteome analysis, including a Lys-C endopeptidase digestion step prior to tryptic digestion, which increased the number of protein identifications and improved reproducibility for on-bead ProteoMiner digestion.

The synovial fluid proteome differentiates between septic and nonseptic articular pathologies.

Articular conditions are common in horses and can result in loss of function, chronic pain and/or inability to work. Common conditions include osteoarthritis, osteochondrosis and synovial sepsis, which can be life-threatening, but despite the high clinical prevalence of these conditions, rapid and specific diagnosis, monitoring and prognostication remains a challenge for practicing veterinarians. Synovial fluid from a range of arthropathies was enriched for low abundance proteins using combinatorial peptide ligand ProteoMiner™ beads and analysed via liquid chromatography-tandem mass spectrometry. Changes in protein abundances were analysed using label-free quantification. Principle component analysis of differentially expressed proteins identified groupings associated with joint pathology. Findings were validated using ELISA. Lactotransferrin (LTF) abundance was increased in sepsis compared to all other groups and insulin-like growth factor-binding protein 6 (IGFBP6) abundance decreased in sepsis compared to other disease groups. Pathway analysis identified upregulation of the complement system in synovial joint sepsis and the downregulation of eukaryotic translation initiation factors and mTOR signalling pathways in both OA and OC compared to the healthy group. Overall, we have identified a catalogue of proteins which we propose to be involved in osteoarthritis, osteochondrosis and synovial sepsis pathogenesis. SIGNIFICANCE: Osteoarthritis, osteochondrosis and synovial sepsis, which can be life-threatening, are common articular conditions in which rapid and specific diagnosis, monitoring and prognostication remains a challenge for practicing veterinarians. This study has identified that the equine synovial fluid proteome exhibits distinctive profile changes between osteoarthritis, osteochondrosis, synovial sepsis and healthy joints. Elevated synovial abundance of lactotransferrin and decreased insulin-like growth factor-binding protein 6 were both found to distinguish synovial sepsis from all other study groups. Thus, these protein markers may have a future role in clinical practice to enable an earlier and reliable diagnosis of synovial sepsis.

Identification and Characterization of Canine Ligament Progenitor Cells and Their Extracellular Matrix Niche.

Ligaments are prone to injury and degeneration in humans and animals, however the healing potential of ligament is poor and current treatment options ineffective. Stem cell-based therapies hold potential for treatment of ligament injuries. This study aimed to characterize a ligament progenitor cell (LPC) population and to identify specific niche components which could promote the survival and function of LPCs. LPCs were isolated from canine cranial cruciate ligament and characterized for clonogenicity, multipotency and marker expression. The extracellular matrix (ECM) composition was characterized by the novel application of a metabolic labeling and mass spectrometry technique. LPCs demonstrated clonogenicity, multipotency, and stem cell marker expression. A number of different collagens, glycoproteins, and proteoglycans were identified in the LPC niche using proteomics. Metabolic labeling of cells demonstrated unique turnover profiles for distinct ECM protein groups, indicating the importance of certain niche components for LPC survival and function. The newly synthesized niche components identified in this study could be exploited to aid identification of LPCs and to promote their survival and function for potential ligament repair strategies.

Communication between the distal interphalangeal joint and the navicular bursa in the horse at Computed Tomography Arthrography.

Diffusion of drugs injected into the distal interphalangeal joint or the navicular (podotrochlear) bursa can influence diagnosis and treatment of foot pain. Previous anatomical and radiographic studies of the communication between these synovial structures have produced conflicting results and did not identify the location of any communication if present. This anatomic study aimed to assess the presence and site of communication between the distal interphalangeal joint and the navicular bursa in the horse by computed tomography arthrography. Sixty-six pairs of cadaver forelimbs were injected with contrast medium into the distal interphalangeal joint and imaged by computed tomography arthrography. The presence of a communication, location of the communication and additional structural changes were assessed. Navicular bursa opacification occurred in 7 distal limbs (5.3%) following distal interphalangeal joint injection. One limb showed a communication through the T-ligament and 6 limbs showed a communication through the distal sesamoidean impar ligament. In 3 cases, the communication through the distal sesamoidean impar ligament was associated with a distal border fragment. Our study showed that communication between the distal interphalangeal joint and navicular bursa is uncommon and inconsistent. Clinically, the presence of a communication could (1) influence the interpretation of diagnostic analgesia of the distal interphalangeal joint or the navicular bursa by facilitating the diffusion of local anaesthetic between these structures; (2) allow the drug and its potential adverse effects to spread from the treated synovial cavity to the non-targeted synovial cavity; (3) be responsible for the failure of joint drainage in the case of sepsis.

Developing a toolkit for the assessment and monitoring of musculoskeletal ageing.

The complexities and heterogeneity of the ageing process have slowed the development of consensus on appropriate biomarkers of healthy ageing. The Medical Research Council-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between researchers and clinicians at the Universities of Liverpool, Sheffield and Newcastle. One of CIMA's objectives is to 'Identify and share optimal techniques and approaches to monitor age-related changes in all musculoskeletal tissues, and to provide an integrated assessment of musculoskeletal function'-in other words to develop a toolkit for assessing musculoskeletal ageing. This toolkit is envisaged as an instrument that can be used to characterise and quantify musculoskeletal function during 'normal' ageing, lend itself to use in large-scale, internationally important cohorts, and provide a set of biomarker outcome measures for epidemiological and intervention studies designed to enhance healthy musculoskeletal ageing. Such potential biomarkers include: biochemical measurements in biofluids or tissue samples, in vivo measurements of body composition, imaging of structural and physical properties, and functional tests. This review assesses candidate biomarkers of musculoskeletal ageing under these four headings, details their biological bases, strengths and limitations, and makes practical recommendations for their use. In addition, we identify gaps in the evidence base and priorities for further research on biomarkers of musculoskeletal ageing.