Models of osteoarthritis: the good, the bad and the promising

Abstract

SummaryOsteoarthritis (OA) is a chronic degenerative disease of diarthrodial joints most commonly affecting people over the age of forty. The causes of OA are still unknown and there is much debate in the literature as to the exact sequence of events that trigger the onset of the heterogeneous disease we recognise as OA.There is currently no consensus model for OA that naturally reflects human disease. Existing ex-vivo models do not incorporate the important inter-tissue communication between joint components required for disease progression and differences in size, anatomy, histology and biomechanics between different animal models makes translation to the human model very difficult. This narrative review highlights the advantages and disadvantages of the current models used to study OA. It discusses the challenges of producing a more reliable OA-model and proposes a direction for the development of a consensus model that reflects the natural environment of human OA.We suggest that a human osteochondral plug-based model may overcome many of the fundamental limitations associated with animal and in-vitro models based on isolated cells. Such a model will also provide a platform for the development and testing of targeted treatment and validation of novel OA markers directly on human tissues.

In vitro and in silico modeling of cellular and matrix-related changes during the early phase of osteoarthritis

“…The reduced model ( Table 5) was obtained as described in the following. For equation (1), it was possible to distinguish between the decrease due to the matrix formation and due to IL-1β by comparing the reduction of the cell density under noninflammatory and inflammatory conditions in the in vitro models. Thus, we could identify the parameters 1 (non-inflammatory conditions) and 9 (inflammatory conditions) separately.…”

“…A 50x magnification overview image of an H&E stained section was taken. The section outline was defined using the Polygonal Selection tool in ImageJ (1). In order to subtract the background (or gap area) the Color Threshold tool was utilized (2).…”

“…The pathogenesis of osteoarthritis (OA) has not been fully understood so far, partly due to the lack of an optimal model system which sufficiently incorporates all aspects of the disease [1,2]. A vast variety of in vivo, ex vivo, in vitro and (to some extent) in silico models for OA already exists, and these all try to mimic the main features of OA pathophysiology including the degradation of extracellular matrix (ECM), inflammation and alterations in cell metabolism, viability and differentiation [3][4][5].…”

Orthotopic Bone Regeneration within 3D Printed Bioceramic Scaffolds with Region‐Dependent Porosity Gradients in an Equine Model

“…However, at the same time, such human pre‐clinical studies constitute end‐stage testing for veterinary application in the animal species involved. [ 17–19 ] Much like humans and unlike other more common large animal models like goats or sheep, horses participate as athletes in competitions, in which bone and osteochondral injuries regularly lead to both great economic losses and serious animal welfare concerns. [ 20–22 ] This makes studies addressing bone regenerative capacity in the horse not only of great interest for human medicine, but also for the equestrian industry and equine health care.…”

CellWell: A micropatterned biphasic nanocomposite platform for culturing chondrocytes

“…Animals models have long been the gold standard for understanding the progression of osteoarthritis. However, they are also associated with concerns of ethical issues regarding the treatment of animals, cost and management issues, anatomical differences of cartilage in animals compared to humans, and age variations of animal species at the time of testing [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25].…”