High expression level of bone degrading proteins as a possible inducer of osteolytic features in pigmented villonodular synovitis.

Protein expression of osteopontin (OPN), osteoprotegerin (OPG), bone sialoprotein (BSP), osteocalcin (OC), RANKL and PTHrP was determined by use of immunohistochemical analysis on tissue arrays (48 cases of PVNS, 20 cases of active (a-RA), non-active rheumatoid arthritis (na-RA), and osteoarthritis (OA)). Additionally, gene expression was analysed using complimentary DNA (cDNA) microarrays. All PVNS cases showed a higher level of both protein and gene expression of RANKL, OPN and BSP in comparison with OA cases. Expression of OPG was not significantly different in PVNS compared to OA. The RANKL/OPG expression ratio was significantly higher in PVNS than in OA. High expressions level of proteins involved in bone degradation in PVNS may promote an intra-osseous propagation of the lesion. This evidence suggests that PVNS might respond to treatment using specific inhibitors of RANKL, OPN and BSP.

Analysis of pigmented villonodular synovitis with genome-wide complementary DNA microarray and tissue array technology reveals insight into potential novel therapeutic approaches.

OBJECTIVE: To characterize the gene expression profile and determine potential diagnostic markers and therapeutic targets in pigmented villonodular synovitis (PVNS). METHODS: Gene expression patterns in 11 patients with PVNS, 18 patients with rheumatoid arthritis (RA), and 19 patients with osteoarthritis (OA) were investigated using genome-wide complementary DNA microarrays. Validation of differentially expressed genes was performed by real-time quantitative polymerase chain reaction and immunohistochemical analysis on tissue arrays (80 patients with PVNS, 51 patients with RA, and 20 patients with OA). RESULTS: The gene expression profile in PVNS was clearly distinct from those in RA and OA. One hundred forty-one up-regulated genes and 47 down-regulated genes were found in PVNS compared with RA, and 153 up-regulated genes and 89 down-regulated genes were found in PVNS compared with OA (fold change > or = 1.5; Q < or = 0.001). Genes differentially expressed in PVNS were involved in apoptosis regulation, matrix degradation, and inflammation (ALOX5AP, ATP6V1B2, CD53, CHI3L1, CTSL, CXCR4, HSPA8, HSPCA, LAPTM5, MMP9, MOAP1, and SPP1). CONCLUSION: The gene expression signature in PVNS is similar to that of activated macrophages and is consistent with the local destructive course of the disease. The gene and protein expression patterns suggest that the ongoing proliferation in PVNS is sustained by apoptosis resistance. This result suggests the possibility of a potential novel therapeutic intervention against PVNS.