Background and Significance

Osteoarthritis is the most common musculoskeletal disease in developed countries. It is characterized by progressive degradation of articular cartilage that leads to joint space narrowing, subchondral sclerosis, osteophyte and cyst formation, and eventually loss of joint function. While OA can be secondary to various factors, the majority of cases are considered primary. Certain OA forms have long been known to have a genetic component. Recent studies have confirmed these findings and indicated a significant role for genetic factors in primary OA.


Lumbar disc disease, characterized by disc herniation and sciatica, is a common musculoskeletal disorder with a prevalence of about 5% in a Finnish population-based cohort. Early epidemiological studies suggested that low back syndromes are mainly caused by environmental and anthropometric factors such as occupational load, back injuries, height and obesity. However, some investigators reported a considerable familial predisposition to early onset sciatica and disc herniation, and more recent epidemiological studies indicate that at least disc degeneration, which precedes disc herniation, and low back pain may be explained primarily by genetic influences.


Primary OP is usually diagnosed as either osteogenesis imperfecta or juvenile idiopathic osteoporosis. Low-density lipoprotein receptor-related protein 5 (LRP5) has recently been shown to affect bone mass accrual during growth. Homozygous inactivating LRP5 mutations cause autosomal recessive OP-pseudoglioma syndrome (OPPG), characterised by severe juvenile-onset OP and congenital or early-onset blindness, and targeted Lrp5 disruption produces postnatal OP in mice. On the other hand, gain-of-function LRP5 mutations have been shown to result in increased Wnt signalling and high bone mass by impairing the action of a normal Wnt antagonist, Dickkopf-1 (Dkk-1). LRP5 acts as a co-receptor for Wnts and this signalling pathway is important in the regulation of bone mass and may have a role in primary OP.


In addition to the studies of genetic susceptibility to common musculoskeletal diseases, we participate in the molecular diagnostics of Stickler (OMIM 108300, 604841, 184840) and Marshall (OMIM 154780) syndromes as part of the European Skeletal Dysplasia Network ( These are clinically overlapping dominantly inherited disorders characterised by midfacial hypoplasia, high myopia and a sensorineural hearing deficit. Stickler syndrome is classified into three subtypes based on ocular phenotype and molecular linkage and mutations are found in at least three genes (COL2A1, COL11A1 and COL11A2). In the area of common disorders affecting hearing, we are interested in genetic susceptibility to Ménière’s disease (MD), an inner ear condition with vertigo, tinnitus and sensorineural hearing loss.

Viimeksi päivitetty: 28.10.2016