Identification of important interactions between subchondral bone ...

3.2.3 In vivo
CHAPTER 3: Overview of OA models
Animal models are commonly used for investigating pathology that resembles the human disease
of interest. These in vivo animal models can often follow preliminary in vitro or ex vivo studies (fig.
11), which need their results to be confirmed in an in situ setting 7,19 . Furthermore, the complex
changes in the joint-tissue of OA patients may take decades to develop and the need to
investigate the early changes in robust and valid in vivo models has necessitated the use of living
animals in experiments. A range of animal models of OA have been developed, such as
spontaneous, surgically induced, and transgenic animal models. These models are not perfect, as
species are not alike, but the models offer the opportunity to display many of the pathologic
features that characterize the human disease. For example, transgenic mice with mutations in
collagen type II develops OA-like changes with age 20,21 , whereas surgically removed menisci can
be observed to induce osteophyte formation, cartilage fibrillation, loss of proteoglycans, and
cellular clustering within few weeks 22,23 . Moreover, several species spontaneously develop OA,
which highly resembles human OA, although these models are relatively slow to develop the
disease 24,25 .
To summarize the advantages, animal models can be used to study pathologic
events representing early OA in human patients, and they are applicable for investigation of the
effects of a variety of agents on the progression of the disease. Furthermore, only animal models
can show altered mental behaviour or catch potential side-effect from a drug (other tissues). One
obvious disadvantage of the in vivo animal models is the potential differences in tissue response
between animals and humans. Eventually, phase-trials of a potential drug would demonstrate the
effect or lack of effect in humans. Another important disadvantage is the ethical aspect of using
living animals, which will not be discussed further in this thesis. Below is a table with the
different pre-clinical models of cartilage.
Table 2. Comparison of different cartilage pre-clinical models. The advantages and disadvantages of the in
vitro, ex vivo and in vivo models are outlined in the table, which makes it easy to compare to each other. Adapted
with modifications from Sondergaard 26 .
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