Translating genomics into mechanisms of disease: Osteoarthritis.
Osteoarthritis (OA) is the most common age-related arthritic disorder and is characterized by aberrant extracellular matrix (ECM) content and surface disruptions that range from fibrillation, clefting and delamination, leading to articular surface erosion. Worldwide, over 20% of the population is affected with OA and 80% of these patients have limitations in movement, whereas 25% experience inhibition in major daily activities of life. OA is the most common disabling arthritic disease; nevertheless, no disease-modifying treatment is available except for the expensive total joint replacement surgery at end-stage disease. Lack of insight into the underlying pathophysiological mechanisms of OA has considerably contributed to the inability of the scientific community to develop disease-modifying drugs. To overcome this critical barrier, focus should be on translation of identified robust gene deviations towards the underlying biological mechanisms.
Dept. Medical Statistics and Bioinformatics, Section Molecular Epidemiology, Leiden University Medical Centre, LUMC Post-zone S-05-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: n.bomer@lumc.nl.
Nils
N
Bomer
Dept. Medical Statistics and Bioinformatics, Section Molecular Epidemiology, Leiden University Medical Centre, LUMC Post-zone S-05-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: W.den_Hollander.MOLEPI@lumc.nl.
Wouter
W
den Hollander
Dept. Medical Statistics and Bioinformatics, Section Molecular Epidemiology, Leiden University Medical Centre, LUMC Post-zone S-05-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: Y.F.M.Ramos@lumc.nl.
Yolande F M
YF
Ramos
Dept. Medical Statistics and Bioinformatics, Section Molecular Epidemiology, Leiden University Medical Centre, LUMC Post-zone S-05-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: i.meulenbelt@lumc.nl.
Ingrid
I
Meulenbelt
D002358:Cartilage, Articular / Q000503:physiopathology*; D023281:Genomics; D006801:Humans; D010003:Osteoarthritis / Q000235:genetics / Q000503:physiopathology*
DIO2 gene; Functional studies; Genomic profiling; Mechanisms; Osteoarthritis; Thyroid signalling