ABSTRACT
Teaching histology, through virtual microscopy in educational strategies, undeniably moved towards the digitization and distancing of teaching. The setting up of the Massive Open Online Course (MOOC) entitled "Introduction to Histology: exploring the tissues of the human body" made it possible to exploit the potential to share digital resources with a wider audience while being integrated into the teaching on-campus students. This article described the pedagogical choices prevailing during the design of the MOOC and its combination with face-to-face sessions to achieve specific learning outcomes. The pedagogical alignment of learning outcomes described according to their cognitive levels, with online and face-to-face learning activities and evaluation methods has been demonstrated. The impact of such a blended design into an academic program has been ascertained using perception and performance data. Student satisfaction and engagement as well as motivational cues were identified. The level of performance was maintained in the educational strategy implemented and made it possible to achieve the objectives expected by the teachers. The benefits of integrating a MOOC with classroom-based teaching were highlighted, as well as barriers that could hinder the successful implementation.
Subject(s)
Education, Distance , Humans , Education, Distance/methods , Learning , Educational MeasurementABSTRACT
OBJECTIVE: We previously identified an association between bone sialoprotein (BSP) and osteoarthritic (OA) chondrocyte hypertrophy but the precise role of BSP in ostearthritis (OA) has not been extensively studied. This study aimed to confirm the association between BSP and OA chondrocyte hypertrophy, to define its effect on molecules produced by chondrocytes and to analyse its association with cartilage degradation and vascular density at the osteochondral junction. METHOD: Human OA chondrocytes were cultivated in order to increase hypertrophic differentiation. The effect of parathyroid hormone-related peptide (PTHrP), interleukin (IL)-1ß or tumour necrosis factor (TNF)-α on BSP was analysed by real-time reverse transcription polymerase chain reaction (RT-PCR) and western blot. The effects of BSP on OA chondrocytes production of inflammatory response mediators (IL-6, nitric oxide), major matrix molecule (aggrecan), matrix metalloprotease-3 and angiogenic factors (vascular endothelial growth factor, basic fibroblast growth factor, IL-8, and thrombospondin-1) were investigated. BSP was detected by immunohistochemistry and was associated with cartilage lesions severity and vascular density. RESULTS: PTHrP significantly decreased BSP, confirming its association with chondrocyte hypertrophy. In presence of IL-1ß, BSP stimulated IL-8 synthesis, a pro-angiogenic cytokine but decreased the production of TSP-1, an angiogenesis inhibitor. The presence of BSP-immunoreactive chondrocytes in cartilage was associated with the severity of histological cartilage lesions and with vascular density at the osteochondral junction. CONCLUSION: This study supports the implication of BSP in the pathology of OA and suggests that it could be a key mediator of the hypertrophic chondrocytes-induced angiogenesis. To control chondrocyte hypertrophic differentiation is promising in the treatment of OA.
Subject(s)
Chondrocytes/pathology , Integrin-Binding Sialoprotein/metabolism , Osteoarthritis, Knee/pathology , Aggrecans/metabolism , Blotting, Western , Chondrocytes/metabolism , Fibroblast Growth Factor 2/metabolism , Humans , In Vitro Techniques , Interleukin-1beta/pharmacology , Interleukin-6/metabolism , Interleukin-8/metabolism , Matrix Metalloproteinase 3/metabolism , Nitric Oxide/metabolism , Osteoarthritis, Knee/metabolism , Parathyroid Hormone-Related Protein/pharmacology , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Thrombospondin 1/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Vascular Endothelial Growth Factors/metabolismABSTRACT
OBJECTIVE: The aim of this study was to investigate the link between the hypertrophic phenotype of chondrocytes and angiogenesis in osteoarthritis (OA) and more particularly to demonstrate that OA hypertrophic chondrocytes potentially express a phenotype promoting angiogenesis through the expression of factors controlling endothelial cells migration, invasion and adhesion. METHOD: Human OA chondrocytes were cultivated in alginate beads in medium supplemented with 10% fetal bovine serum (FBS) to induce chondrocyte hypertrophy. The hypertrophic phenotype was characterized throughout 28 days of culture by measuring the expression of specific genes and by a microscopic observation of cellular morphology. The effect of media conditioned by OA hypertrophic chondrocyte on endothelial cells migration, invasion and adhesion was evaluated in functional assays. Moreover, hypertrophic OA chondrocytes were tested for the expression of angiogenic factors by real-time RT-PCR. RESULTS: Specific markers of hypertrophy and observation of cellular morphology attested of the hypertrophic phenotype of chondrocytes in our culture model. Functional angiogenesis assays showed that factors produced by hypertrophic chondrocytes stimulated migration, invasion and adhesion of endothelial cells. Among the evaluated angiogenic factors, bone sialoprotein (BSP) was the most highly upregulated in hypertrophic chondrocytes. The inhibition of endothelial cell adhesion by a GRGDS peptide confirmed the implication of RGD domain proteins, like BSP, in hypertrophic chondrocyte-induced adhesion of endothelial cells. CONCLUSION: Hypertrophic differentiation of chondrocyte may promote angiogenesis. Our findings established the relation of BSP with OA chondrocyte hypertrophy and suggested that this factor could constitute a potential target to control cartilage neovascularisation in OA.
Subject(s)
Cartilage, Articular/metabolism , Chondrocytes/pathology , Endothelial Cells/physiology , Neovascularization, Pathologic/genetics , Osteoarthritis/genetics , Angiopoietin-1/genetics , Angiopoietin-1/metabolism , Cartilage, Articular/cytology , Cell Adhesion , Cell Movement , Cells, Cultured , Chondrocytes/metabolism , Fibroblast Growth Factor 2/genetics , Fibroblast Growth Factor 2/metabolism , Gene Expression Regulation , Humans , Hypertrophy , Integrin-Binding Sialoprotein/genetics , Integrin-Binding Sialoprotein/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/physiopathology , Nerve Growth Factor/genetics , Nerve Growth Factor/metabolism , Osteoarthritis/metabolism , Osteoarthritis/physiopathology , Osteopontin/genetics , Osteopontin/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Thrombospondin 1/genetics , Thrombospondin 1/metabolism , Thrombospondins/genetics , Thrombospondins/metabolism , Up-Regulation , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
The subchondral bone is involved in the pathophysiology of osteoarthritis (OA), both by biochemical and mechanical pathways. Overloaded OA subchondral bone osteoblasts express a pro-angiogenic and pro-inflammatory phenotype which contributes to explain the structural changes (sclerosis and bone marrow lesion) visible in OA subchondral bone. Further, microfractures and conjonctivo-vascular structures constitute exchange routes between bone and the overlying cartilage for mediators produced by osteoblasts. This narrative review describes these physiopathological mechanisms and identifies possible therapeutic targets for pharmacological modalities.
Subject(s)
Bone and Bones/pathology , Osteoarthritis/pathology , Bone Diseases, Metabolic/etiology , Cartilage, Articular/pathology , Humans , Obesity/complications , Osteoarthritis/complications , Osteoblasts/physiology , Phenotype , Sclerosis , Stress, MechanicalABSTRACT
Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. A hallmark of the disease is progressive degeneration of articular cartilage and subsequent joint space narrowing. However, OA is a complex disease not limited to cartilage degeneration, but involving also synovial membrane and subchondral bone, thereby presenting alternatives approaches for treatment. In this paper, we propose a short review of the recent advances in the understanding of the role played by subchondral bone in OA.
