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