Morphological changes in articular cartilage due to static compression: polarized light microscopy study.

We studied the deformation of the extracellular matrices in articular cartilage using a new compression-preservation method in histology. A Hoffman clamp was used to compress the tissue, which remained throughout the paraffin procedure and was removed from the embedded tissue block just before microtoming. Then 14 cartilage-bone blocks from 2 canine humeri were compressed for various strain levels from 5% to 65%. The histological sections were studied using a polarized light microscope, which generated a pair of two-dimensional maps of the fibril orientation (angle) and fibril organization (retardance) for each section. Results were 3-fold. One there was little change in the angle and retardance profiles of the tissue for strain levels 0-15% and a significant change in these profiles for strain levels 15% and above. Two for higher compression, more fibrils became aligned parallel to the articular surface; and three at approximately 30% strain, a second "transitional zone" was formed in the deep part of the tissue. We concluded that this novel compression procedure can be used effectively to study the altered architecture of the collagen matrix in compressed cartilage.

Differential involvement of MMP-2 and VEGF during muscle stretch- versus shear stress-induced angiogenesis.

Capillary growth in skeletal muscle occurs via the dissimilar processes of abluminal sprouting or longitudinal splitting, which can be initiated by muscle stretch and elevated shear stress, respectively. The distinct morphological hallmarks of these types of capillary growth suggest that discrete sets of angiogenic mediators play a role in each situation. Because proteolysis and proliferation are two key steps associated with capillary growth, we tested whether differences in the regulation of matrix metalloproteinases (MMPs) or VEGF may be associated with the two types of capillary growth. We found significant increases in MMP-2 total protein and percent activation, and membrane type-1 MMP mRNA levels, compared with controls after muscle stretch but not after shear stress stimulation. In contrast, VEGF protein and endothelial cell proliferation increased after either angiogenic stimulus. We observed that MMP-2 regulation occurs independent of VEGF signaling, because VEGF did not induce MMP-2 production or activation in isolated endothelial cells. Our data suggest that the involvement of MMPs in capillary growth is dependent on the nature of the angiogenic stimulus.

Strain differences and inheritance of angiogenic versus angiostatic activity in oestrogen-induced rat pituitary tumours.

In this study we investigated the control of the angiogenic/haemorrhagic phenotype of oestrogen-induced rat pituitary tumours of an F1 hybrid (F1) of Fischer 344 (F344) (tumour susceptible) and Brown Norway (tumour resistant) strains. F1 forms a pituitary tumour upon chronic oestrogen treatment, but microvessel count (MVC) is no greater than untreated. In other words, F1 MVC keeps pace with tissue growth during growth of an oestrogen-induced tumour. On the other hand, F344 showed a significant increase in MVC (P = 0.002) upon chronic oestrogen treatment during growth of a large pituitary tumour. F1 control vasculature showed features intermediate between the parent strains, while oestrogen-treated F1 pituitary has pronounced changes commensurate with vascular remodelling or angiogenic activity, along with regressive changes. In addition, oestrogen-treated F1 does not form the haemorrhagic lakes characteristic of oestrogen-treated F344. We conclude that F1, which has a 50-50 genetic composition of the tumour susceptibility and tumour resistance alleles, shows loss of angiostatic activity in the absence of an effective angiogenic stimulus. As a result it is unable to make the 'switch' to the angiogenic phenotype.