Cindy Boer

12 | Chapter 1.1 The problem Osteoarthritis is one of the world’s oldest diseases, and yet no curative treatments are available. Osteoarthritis is the most common chronic degenerative joint disease world- wide and has been present throughout history, evidenced by the presence of osteoar- thritis in the fossilized ankle bones of Iguanodon bernissartensis ( Figure 1 ), the first ever recognized dinosaur species[1, 2] . Not only dinosaur fossils have been found with osteoarthritis, also early bird ancestor (Caudipteryx )[3], marsupial ( Diprotodon ) [4], and mammal ( Glyptodont and Canis dirus )[5, 6] fossils are known. In fact, probably the first common ancestor to all bony vertebrates ( Eutelestomi ) could have been affected by os-teoarthritis[7]. Early man was also plagued by osteoarthritis. The disease is one of the most common features seen in archeo-paleontology[8], with evidence from Neander-thals[9], early inhabitants of America[10], Egyptian mummies[11, 12], medieval citi-zens and knights[13] ( Figure 1 ) , up to the modern day where 4-5% of the entire world population has at least one joint affected by OA[2]. Symptoms of the disease are stiffness, loss of mobility and loss of function in the affected joint, with pain described as the most dominant and disabling symptom of the disease[14]. Not surprisingly, osteoarthritis is the single biggest cause for joint pain and disability worldwide[2]. Currently osteoarthritis is the third most rapidly grow- ing chronic disease worldwide[2]. Combined with the global increase in risk factors for osteoarthritis (aging, joint injury and obesity), the impact and burden of osteoarthri- tis will only continue to rise. Yet, no curative treatments for osteoarthritis are known, and much of the pathology of osteoarthritis remains a mystery. Thus, it is high time to unravel the mysteries surrounding osteoarthritis, a disease plaguing its hosts for over hundreds of millions of years. ► Figure 1: A brief Timeline of Osteoarthritis . Osteoarthritis is one of the oldest known diseases in the world; the first known bony vertebrate ( Guiyu onerios ) might already have had osteoarthritis. Fos- sil evidence dates back to the cretaceous (~125 Ma), and ample evidence of the disease exists in the Pleistocene, where even the H. neanderthalensis was affected by osteoarthritis. Osteoarthritis is seen throughout human history, from ancient Egypt, Greece (where Hippocrates first described signs of the disease) and medieval Europe to the modern day, however it was not until 1889 that osteoarthritis got its name. With the discovery of the helix structure of DNA, genetic research into osteoarthritis started in full; from family studies, twins studies, linkage scans and the first Genome-wide association study to the start of this thesis on “ Osteoarthritis; Genotypes and phenotypes in all their complexity ”. Ma: Mega annum , ka: kilo annum, annum : one year. BC: Before Christ, AD: Anno Domini