Down-regulation of the GTPase RhoB might be involved in the pre-apoptotic phenotype of osteoarthritic chondrocytes.
Anabolic activity, phenotypic alterations, and in particular survival of the chondrocytes are essential for the maintenance of proper articular cartilage and appears to fail during osteoarthritic cartilage degeneration. In this study, we investigated the presence and expression of RhoB in adult human articular cartilage and its regulation in osteoarthritic cartilage as well as in chondrocytes in vitro. RhoB belongs to the family of small GTPases, which are thought to be involved in a large range of activities important for eukaryotic cells. Conventional and quantificative PCR analysis showed significant levels of RhoB expression in normal articular cartilage. Immunolocalization and confocal laser scanning microscopy showed strong cytoplasmic signals for RhoB in normal chondrocytes. In osteoarthritic cartilage, a significantly lower expression of RhoB was detectable. In vitro experiments showed a quick (and transient) up-regulation of RhoB after stimulation with interleukin-1beta and serum. Our study suggests that RhoB is constitutively expressed and essential for adult articular chondrocytes, but significantly down-regulated in osteoarthritic chondrocytes. One intriguing speculation might be that the down-regulation of RhoB in osteoarthritic chondrocytes is at least partly a prerequisite for the sustained pre- or para-apoptotic phenotype of osteoarthritic chondrocytes, because RhoB is known to be one important molecule in the induction of apoptotic cell death in response to DNA damage and osteoarthritic chondrocytes are known to have significant DNA damage. Alternatively, RhoB could be involved in the activation or deactivation and the destabilization of the functional phenotype of chondrocytes in osteoarthritic joint degeneration Thirdly, RhoB is associated with the cell cycle, which is re-initiated in osteoarthritis.
Gebhard
Pia M
PM
Cartilage Research, Department of Pathology, University of Erlangen-Nurnberg, FRG.
Söder
Stephan
S
Bau
Brigitte
B
Aigner
Thomas
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D018613:Microscopy, Confocal; D008875:Middle Aged; D010003:Osteoarthritis / Q000473:pathology*; D010641:Phenotype; D014018:Tissue Distribution; D020743:rhoB GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D007375:Interleukin-1; D020743:rhoB GTP-Binding Protein