Estrogen receptor beta and truncated variants enhance the expression of transfected MMP-1 promoter constructs in response to specific mechanical loading

Background

Joint diseases such as osteoarthritis (OA) predominantly afflict post-menopausal women, suggesting a pertinent role for female hormones. Estrogen receptor beta (ER-β) has been detected in connective tissues of the knee joint suggesting that these tissues are responsive to the hormone estrogen. Matrix metalloproteinase-1 (MMP-1) activity contributes to cartilage degradation, a key factor leading to OA development in synovial joints. Two polymorphic forms of MMP-1 exist due to a deletion/insertion of the guanine residue in the promoter, and the 2G allelic variant of MMP-1 exhibits more activity than the 1G allele. Previous studies have demonstrated that the polymorphic forms of the human MMP-1 are influenced by the modulating effects of estrogen receptor isoforms. In addition to hormonal influences, physiological factors such as altered mechanical loading are also contributory features of OA. In the present study, the combined influence of biomechanical and hormonal variables on the activity of MMP-1 isoforms was evaluated. We hypothesized that the combined effects of ER-β and sheer stress will differentially activate the two allelic forms of MMP-1 in a hormone-independent manner.

Methods

HIG-82 synoviocytes were transiently transfected with 1G or 2G alleles (±) ER-β and subjected to either shear or equibiaxial stress. Next, 1G/2G promoter activity was measured to determine the combined influence of physiological stimuli. Truncated ER-β constructs were used to determine the importance of different domains of ER-β on 1G/2G activation.

Results

The 2G allele exhibited a constitutively higher activity than the 1G allele, which was further increased when the transfected cells were subject to shear stress, but not equibiaxial stress. Moreover, the combination of ER-β and shear stress further increased the activity levels of the 1G/2G allelic variants. Additionally, select AF-2 truncated ER-β variants led to increased activity levels for the 2G allele, indicating the AF-1 domain was likely involved in the response to mechanical stimulation.

Conclusions

These results suggest that the 1G/2G alleles of MMP-1 are influenced by specific mechanical stimuli like shear stress, as well as the ER-β receptor. These findings contribute to the potential allelic involvement in connective tissue diseases such as OA in females compared to males.

     

Diagnostic and prognostic value of immunohistological bone marrow examination: results in 212 patients with lymphoproliferative disorders

Cryostat sections of 246 consecutive bone marrow biopsies from 212 patients with lymphoproliferative disease were investigated using a panel of monoclonal antibodies (MOAb's) and an immunoperoxidase technique. Bone marrow involvement was demonstrated by immunohistological examination in 121/160 patients (76%) with non-Hodgkin lymphomas (NHL) and 16/23 patients (70%) with plasma cell malignancies; the definite immunological diagnosis could be performed in 77% and 88%, respectively. Reactivity with the MoAb Ki-67 correlated with clinical parameters: in all cases exhibiting more than 5% positive cells an unfavourable course was seen, independent of the histological subtype. Another MoAb of potential prognostic relevance is KiM 4 b, which reacts with follicular dendritic cells (FDC). Besides the presence of FDC in germinal center tumors (CB/CC and CC-NHL) we found FDC in a minority of cases with B-CLL (5/44) and IC lymphoma (4/18). In the latter group 3/4 patients showed a favourable clinical course (vs 2/14 without FDC). The MoAb Tü 1 could discriminate between the lymphoplasmocytoid (11/12 positive) and the lymphoplasmocytic (0/6 positive) subtype of IC lymphoma and has proven of diagnostic importance. Expression of IL-2 receptors, detected by MoAb anti-Tac (CD 25), was demonstrated on leukemic cells from patients with hairy cell leukemia (100%), B-CLL (82%), IC (61%), CC (50%) and CB/CC lymphoma (50%). A considerable number of reactive T-lymphocytes (5%-60% of tissue cells) were identified among the neoplastic B cells with a predominance of CD4+ cells in most cases with NHL, whereas the CD4+/CD8+ ratio was significantly lower in myelomas and non-infiltrated bone marrows. The potential meaning of these findings is discussed. The immunohistological bone marrow analysis represents an important additional method in the diagnostic procedures of lymphoproliferative diseases involving the bone.     

Ein neues Vorkommen vonChelidonium majus L. var.fumariifolium (DC.) KOCH in Graz

Zusammenfassung In Graz wurde ein neues Vorkommen vonC. majus L. var.fumariifolium (DC.)Koch beobachtet. Die Chromosomenzahl in den meristematischen Zellen der Samenanlagen und der Sproßgewebe betrug 2n=12. In den Makrosporen-Mutterzellen wurde die Zahln=6 ermittelt. Es ist dies die gleiche Zahl wie beiC. majus L. var.majus und wie beiC. majus L. var.tenuifolium Retz.     

Anthozyan-Idioblasten der Frucht vonPolygonatum verticillatum

Ohne ZusammenfassungHerrn Univ.-Prof. Dr. AdolfSperlich zum 80. Geburtstag gewidmet.     

Kern-Kristalloide in Stomata-Zellen?

Zusammenfassung Eiwei\kristalloide (Spindeln) sind bisher im Cytoplasma der Schlie\zellen nicht gefunden worden. Auch im Zellkern der Schlie\zellen fehlen die Kristalloide in der Regel. Eine Ausnahme bilden die Schlie\zellen vonCampanula-Alten, ihre Kerne weisen stets Eiwei\spindeln auf. Das Fehlen der Eiwei\kristalloide im Cytoplasma und meist auch im Karyoplasma der Schlie\zellen ist ein bisher kaum beachtetes Symptom der stoffwechselphysiologischen Eigenheit (Idioblastennatur) der Stomatazellen.     

Schriftenschau

Ohne Zusammenfassung