Identification of important interactions between subchondral bone ...

CHAPTER 3
Overview of OA models
CHAPTER 3: Overview of OA models
This Overview aims to introduce some of the different pre-clinical models used today to
investigate the pathogenesis of OA with emphasis on the ex vivo model. In brief, the complexity
and advantages/disadvantages of the different models and the motivation for developing the
femur head model (PAPER I) are described. Further, the controls used in previous ex vivo models
are evaluated in order to understand the selection of these controls for the present femur head
model (PAPER I).
3.1 Pre-clinical models
Clinical studies of OA in humans are expensive and very time consuming. Furthermore, clinical
studies do not provide information about processes and mechanisms involved in pathogenic OA-
tissues, which could be key information to prevent or stop the ongoing development of the
disease. For these and ethical reasons, pre-clinical models are commonly used to investigate the
metabolism of healthy/diseased bone or cartilage, which can be classified according to their
complexity (fig. 11):
In vitro; monolayer or pellet systems of isolated cells
Ex vivo explants cultures, in which the cells are held in their natural matrix
In vivo animal models; such as spontaneous, surgically induced, or transgenic, which resemble
the human disease (apart from the species/origin)
Each of these models has advantages and disadvantages depending on the purpose of the
investigation. In the following section, the methodology behind the three models will be described
in brief in relation to OA with main focus on the ex vivo model.
Fig. 11. The different types of pre-clinical models. In an in vitro model, cells are isolated from their natural
environments, which may cause them to change phenotype during culture. In an ex vivo model, the cells are
maintained in their natural environments, but lack systemic influence (pressure, blood supply etc.). In in vivo
models, the cells are maintained in their natural environment and host. The figure was produced by Madsen, S.H.
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