Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC) therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion, and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum, and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities, and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple “one size fits all,” but more likely an array of solutions that need to be applied systematically to achieve regeneration of a biomechanically competent repair tissue

Glucose: an energy currency and structural precursor in articular cartilage and bone with emerging roles as an extracellular signaling molecule and metabolic regulator

In the skeletal system glucose serves as an essential source of energy for the development, growth, and maintenance of bone and articular cartilage. It is particularly needed for skeletal morphogenesis during embryonic growth and fetal development. Glucose is vital for osteogenesis and chondrogenesis, and is used as a precursor for the synthesis of glycosaminoglycans, glycoproteins, and glycolipids. Glucose sensors are present in tissues and organs that carry out bulk glucose fluxes (i.e., intestine, kidney, and liver). The beta cells of the pancreatic islets of Langerhans respond to changes in blood glucose concentration by varying the rate of insulin synthesis and secretion. Neuronal cells in the hypothalamus are also capable of sensing extracellular glucose. Glucosensing neurons use glucose as a signaling molecule to alter their action potential frequency in response to variations in ambient glucose levels. Skeletal muscle and adipose tissue can respond to changes in circulating glucose but much less is known about glucosensing in bone and cartilage. Recent research suggests that bone cells can influence (and be influenced by) systemic glucose metabolism. This focused review article discusses what we know about glucose transport and metabolism in bone and cartilage and highlights recent studies that have linked glucose metabolism, insulin signaling, and osteocalcin activity in bone. These new findings in bone cells raise important questions about nutrient sensing, uptake, storage and processing mechanisms and how they might contribute to overall energy homeostasis in health and disease. The role of glucose in modulating anabolic and catabolic gene expression in normal and osteoarthritic chondrocytes is also discussed. In summary, cartilage and bone cells are sensitive to extracellular glucose and adjust their gene expression and metabolism in response to varying extracellular glucose concentrations

COVID-19, Companion Animals, Comparative Medicine, and One Health

AbstractThe COVID-19 pandemic in 2020 has stimulated open collaboration between different scientific and clinical disciplines like never before. Public and private partnerships continue to form in order to tackle this unprecedented global challenge. This paper highlights the importance of open collaboration and cooperation between the disciplines of medicine, veterinary medicine, and animal health sciences in the fight against COVID-19. Since the pandemic took the whole world by surprise, many existing drugs were rapidly repurposed and tested in COVID-19 clinical trials and some of the trials are revealing promising results, it is clear that the long-term solution will come in the form of vaccines. While vaccines are being developed, the antiviral agent Remdesivir (RDV, GS-5734) is being repurposed for use in human clinical trials but this is being done without acknowledging the significant efforts that went into development for treating cats with feline infectious peritonitis (FIP), a highly fatal immune-mediated vasculitis in cats which is caused by a feline coronavirus. There are many other antiviral drugs and immune modulating treatments that are currently being trialed that have animal health origins in terms of discovery and clinical development. Closer collaboration between the animal health and human health sectors is likely to accelerate progress in the fight against COVID-19. There is much that we do not yet know about COVID-19 and its causative agent SARS-CoV-2 but we will learn and progress much faster if we increase interdisciplinary collaboration and communication between human and animal health researchers and taking a genuine “One Health” approach to this and other emerging viral pathogens. Enhanced knowledge of zoonotic coronaviruses can significantly enhance our ability to fight current and future emerging coronaviruses. This article highlights the acute need for One Health and comparative medicine and the crucial importance of building on and recognizing veterinary research for addressing future human pandemics.Abstract The COVID-19 pandemic in 2020 has stimulated open collaboration between different scientific and clinical disciplines like never before. Public and private partnerships continue to form in order to tackle this unprecedented global challenge. This paper highlights the importance of open collaboration and cooperation between the disciplines of medicine, veterinary medicine, and animal health sciences in the fight against COVID-19. Since the pandemic took the whole world by surprise, many existing drugs were rapidly repurposed and tested in COVID-19 clinical trials and some of the trials are revealing promising results, it is clear that the long-term solution will come in the form of vaccines. While vaccines are being developed, the antiviral agent Remdesivir (RDV, GS-5734) is being repurposed for use in human clinical trials but this is being done without acknowledging the significant efforts that went into development for treating cats with feline infectious peritonitis (FIP), a highly fatal immune-mediated vasculitis in cats which is caused by a feline coronavirus. There are many other antiviral drugs and immune modulating treatments that are currently being trialed that have animal health origins in terms of discovery and clinical development. Closer collaboration between the animal health and human health sectors is likely to accelerate progress in the fight against COVID-19. There is much that we do not yet know about COVID-19 and its causative agent SARS-CoV-2 but we will learn and progress much faster if we increase interdisciplinary collaboration and communication between human and animal health researchers and taking a genuine “One Health” approach to this and other emerging viral pathogens. Enhanced knowledge of zoonotic coronaviruses can significantly enhance our ability to fight current and future emerging coronaviruses. This article highlights the acute need for One Health and comparative medicine and the crucial importance of building on and recognizing veterinary research for addressing future human pandemics

Applications of Proteomics to Osteoarthritis, a Musculoskeletal Disease Characterized by Aging

The incidence of age-related musculoskeletal impairment is steadily rising throughout the world. Musculoskeletal conditions are closely linked with aging and inflammation. They are leading causes of morbidity and disability in man and beast. Aging is a major contributor to musculoskeletal degeneration and the development of osteoarthritis (OA). OA is a degenerative disease that involves structural changes to joint tissues including synovial inflammation, catabolic destruction of articular cartilage and alterations in subchondral bone. Cartilage degradation and structural changes in subchondral bone result in the production of fragments of extracellular matrix molecules. Some of these biochemical markers or “biomarkers” can be detected in blood, serum, synovial fluid, and urine and may be useful markers of disease progression. The ability to detect biomarkers of cartilage degradation in body fluids may enable clinicians to diagnose sub-clinical OA as well as determining the course of disease progression. New biomarkers that indicate early responses of the joint cartilage to degeneration will be useful in detecting early, pre-radiographic changes. Systems biology is increasingly applied in basic cartilage biology and OA research. Proteomic techniques have the potential to improve our understanding of OA physiopathology and its underlying mechanisms. Proteomics can also facilitate the discovery of disease-specific biomarkers and help identify new therapeutic targets. Proteomic studies of cartilage and other joint tissues may be particularly relevant in diagnostic orthopedics and therapeutic research. This perspective article discusses the relevance and potential of proteomics for studying age-related musculoskeletal diseases such as OA and reviews the contributions of key investigators in the field

Investigating impacts of environmental factors on the cycling behavior of bicycle-sharing users

As it is widely accepted, cycling tends to produce health benefits and reduce air pollution. Policymakers encourage people to use bikes by improving cycling facilities as well as developing bicycle-sharing systems (BSS). It is increasingly interesting to investigate how environmental factors influence the cycling behavior of users of bicycle-sharing systems, as users of bicycle-sharing systems tend to be different from regular cyclists. Although earlier studies have examined effects of safety and convenience on the cycling behavior of regular riders, they rarely explored effects of safety and convenience on the cycling behavior of BSS riders. Therefore, in this study, we aimed to investigate how road safety, convenience, and public safety affect the cycling behavior of BSS riders by controlling for other environmental factors. Specifically, in this study, we investigated the impacts of environmental characteristics, including population density, employment density, land use mix, accessibility to point-of-interests (schools, shops, parks and gyms), road infrastructure, public transit accessibility, road safety, convenience, and public safety on the usage of BSS. Additionally, for a more accurate measure of public transit accessibility, road safety, convenience, and public safety, we used spatiotemporally varying measurements instead of spatially varying measurements, which have been widely used in earlier studies. We conducted an empirical investigation in Chicago with cycling data from a BSS called Divvy. In this study, we particularly attempted to answer the following questions: (1) how traffic accidents and congestion influence the usage of BSS; (2) how violent crime influences the usage of BSS; and (3) how public transit accessibility influences the usage of BSS. Moreover, we tried to offer implications for policies aiming to increase the usage of BSS or for the site selection of new docking stations. Empirical results demonstrate that density of bicycle lanes, public transit accessibility, and public safety influence the usage of BSS, which provides answers for our research questions. Empirical results also suggest policy implications that improving bicycle facilities and reducing the rate of violent crime rates tend to increase the usage of BSS. Moreover, some environmental factors could be considered in selecting a site for a new docking station

Are crowdsourced datasets suitable for specialized routing services? Case study of Openstreetmap for routing of people with limited mobility

Nowadays, Volunteered Geographic Information (VGI) has increasingly gained attractiveness to both amateur users and professionals. Using data generated from the crowd has become a hot topic for several application domains including transportation. However, there are concerns regarding the quality of such datasets. As one of the most famous crowdsourced mapping platforms, we analyze the fitness for use of OpenStreetMap (OSM) database for routing and navigation of people with limited mobility. We assess the completeness of OSM data regarding sidewalk information. Relevant attributes for sidewalk information such as sidewalk width, incline, surface texture, etc. are considered, and through both extrinsic and intrinsic quality analysis methods, we present the results of fitness for use of OSM data for routing services of disabled persons. Based on empirical results, it is concluded that OSM data of relatively large spatial extents inside all studied cities could be an acceptable region of interest to test and evaluate wheelchair routing and navigation services, as long as other data quality parameters such as positional accuracy and logical consistency are checked and proved to be acceptable. We present an extended version of OSMatrix web service and explore how it is employed to perform spatial and temporal analysis of sidewalk data completeness in OSM. The tool is beneficial for piloting activities, whereas the pilot site planners can query OpenStreetMap and visualize the degree of sidewalk data availability in a certain region of interest. This would allow identifying the areas that data are mostly missing and plan for data collection events. Furthermore, empirical results of data completeness for several OSM data indicators and their potential relation to sidewalk data completeness are presented and discussed. Finally, the article ends with an outlook for future research study in this area

Physicochemical and biomechanical stimuli in cell-based articular cartilage repair

Articular cartilage is a unique load-bearing connective tissue with a low intrinsic capacity for repair and regeneration. Its avascularity makes it relatively hypoxic and its unique extracellular matrix is enriched with cations, which increases the interstitial fluid osmolarity. Several physicochemical and biomechanical stimuli are reported to influence chondrocyte metabolism and may be utilized for regenerative medical approaches. In this review article, we summarize the most relevant stimuli and describe how ion channels may contribute to cartilage homeostasis, with special emphasis on intracellular signaling pathways. We specifically focus on the role of calcium signaling as an essential mechanotransduction component and highlight the role of phosphatase signaling in this context