Identification of important interactions between subchondral bone ...

2.4 The effect of Glucocorticoids
CHAPTER 2: Introduction
Glucocorticoids (GCs) belongs to a class of steroid hormones that bind to the glucocorticoid
receptor (GR). This receptor is present in almost every vertebrate animal cell and activation of
GRs initiate an up-regulation of the expression of anti-inflammatory proteins and represses the
expression of pro-inflammatory proteins 146 . Consequently, GCs have potent anti-inflammatory
and immunosuppressive properties and are thus part of the feedback mechanism in the immune
system that decreases the inflammation 147,148 . Therefore, GCs are used as drugs to treat
inflammatory conditions such as arthritis (e.g. rheumatoid arthritis), dermatitis, and diseases that
are caused by an overactive immune system (allergies, asthma, and autoimmune diseases) (Table
1) 146,148 . GCs are also administered as post-transplant immunosuppressants to prevent any acute
transplant rejection and graft-versus-host disease. However, they do not prevent an infection and
they also inhibit later reparative processes 146 .
Treatment with GCs has many diverse effects, including potentially harmful side
effects (Table 1) 146 . Excessive GC levels resulting from administration as a drug affect many
systems, including inhibition of bone formation, suppression of calcium absorption and delayed
wound healing 148 . With respect to OA, intra-articular injections of GCs appear to have a reducing
effect on inflammation and pain 149 . Unfortunately, prolonged GC therapy results in GC-induced
osteoporosis 150 . Thus, to treat OA, GCs without detrimental effects on bone are needed.
The major endogenous GC in humans is cortisol, which was first used
therapeutically for rheumatoid arthritis by Hench and co-workers in 1949 151 . Since then, a large
number of synthetic compounds with GC activity have been developed for therapeutic use. They
differ in pharmacokinetics and pharmacodynamics 152 . The potencies and effects of some of the
synthetic glucocorticoids used for treatment are described in Table 1.
Table 1. Synthetic glucocorticoids and their effects/side-effects. Most of the synthetic glucocorticoids have
the same general effect (anti-inflammatory and immunosuppressive effects), but the potency and specificity for
certain diseases vary 153,152 .
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