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 ≥1.5; Q ≤ 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.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The sedimentary infill of glacially overdeepened valleys
(i.e., structures eroded below the fluvial base level) is an excellent but
yet underexplored archive with regard to the age, extent, and ...nature of past glaciations. The ICDP project DOVE (Drilling Overdeepened Alpine Valleys) Phase 1 investigates a series of drill cores from glacially overdeepened troughs at several locations along the northern front of the Alps. All sites
will be investigated with regard to several aspects of environmental
dynamics during the Quaternary, with focus on the glaciation, vegetation,
and landscape history. Geophysical methods (e.g., seismic surveys), for
example, will explore the geometry of overdeepened structures to better
understand the process of overdeepening. Sedimentological analyses combined
with downhole logging, analysis of biological remains, and state-of-the-art
geochronological methods, will enable us to reconstruct the erosion and
sedimentation history of the overdeepened troughs. This approach is expected
to yield significant novel data quantifying the extent and timing of Middle
and Late Pleistocene glaciations of the Alps. In a first phase, two sites
were drilled in late 2021 into filled overdeepenings below the
paleolobe of the Rhine Glacier, and both recovered a trough filling composed
of multiphase glacial sequences. Fully cored Hole 5068_1_C reached a depth of 165 m and recovered 10 m molasse bedrock at the base. This hole will be used together with two flush holes (5068_1_A, 5068_1_B) for further geophysical cross-well experiments. Site 5068_2 reached a depth of 255 m
and bottomed out near the soft rock–bedrock contact. These two sites are
complemented by three legacy drill sites that previously recovered filled
overdeepenings below the more eastern Alpine Isar-Loisach, Salzach, and Traun paleoglacier lobes (5068_3, 5068_4, 5068_5). All analysis and
interpretations of this DOVE Phase 1 will eventually lay the ground for an
upcoming Phase 2 that will complete the pan-Alpine approach. This follow-up
phase will investigate overdeepenings formerly occupied by paleoglacier
lobes from the western and southern Alpine margins through drilling sites in France, Italy, and Slovenia. Available geological information and
infrastructure make the Alps an ideal area to study overdeepened structures;
however, the expected results of this study will not be restricted to the
Alps. Such features are also known from other formerly glaciated mountain
ranges, which are less studied than the Alps and more problematic with
regards to drilling logistics. The results of this study will serve as
textbook concepts to understand a full range of geological processes
relevant to formerly glaciated areas all over our planet.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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