Evidence of somatic mutations in osteoarthritis.
We examined, cytogenetically and by in situ hybridization (ISH) techniques, the synovia, osteophytes, and articular cartilage from 32 patients with pronounced osteoarthritis (OA), a prevalent form of arthropathy characterized by progressive reduction of articular cartilage, and synovial samples from 17 control patients. In short-term cultures, clonal chromosome aberrations, in particular the gain of chromosomes 7 (+7) and 5 (+5), were found to be strongly associated with OA. These aberrations were found in almost 90% of the cultures from synovia and osteophytes, whereas only 1/11 synovial samples from joints unequivocally unaffected by OA had cells with +5 or +7. The in vivo nature of trisomy 7 was demonstrated by ISH on uncultured cells, and serial passaging showed that cells with +7 had a proliferative advantage in vitro. Thus, the combined data indicate that cells with somatic mutations appear early and may be influential in the disease process leading to OA.
Mertens
F
F
Department of Clinical Genetics, University Hospital, Lund, Sweden.
Pålsson
E
E
Lindstrand
A
A
Toksvig-Larsen
S
S
Knuutila
S
S
Larramendy
M L
ML
el-Rifai
W
W
Limon
J
J
Mitelman
F
F
Mandahl
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D002897:Chromosomes, Human, Pair 7; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics*; D013583:Synovial Membrane / Q000737:chemistry; D014314:Trisomy