Expression of macrophage elastase (MMP12) in rat tail intervertebral disc and growth plate after asymmetric loading.

OBJECTIVES: The aim of this study was to examine whether asymmetric loading influences macrophage elastase (MMP12) expression in different parts of a rat tail intervertebral disc and growth plate and if MMP12 expression is correlated with the severity of the deformity. METHODS: A wedge deformity between the ninth and tenth tail vertebrae was produced with an Ilizarov-type mini external fixator in 45 female Wistar rats, matched for their age and weight. Three groups were created according to the degree of deformity (10°, 30° and 50°). A total of 30 discs and vertebrae were evaluated immunohistochemically for immunolocalisation of MMP12 expression, and 15 discs were analysed by western blot and zymography in order to detect pro- and active MMP12. RESULTS: No MMP12 expression was detected in the nucleus pulposus. Expression of MMP12 in the annulus progressively increased from group I to groups II and III, mainly at the concave side. Many growth plate chondrocytes expressed MMP12 in the control group, less in group I and rare in groups II and III. Changes in cell phenotype and reduction of cell number were observed, together with disorganisation of matrix microstructure similar to disc degeneration. ProMMP12 was detected at the area of 54 kDa and active MMP12 at 22 kDa. CONCLUSIONS: Expression of MMP12 after application of asymmetric loading in a rat tail increased in the intervertebral disc but decreased in the growth plate and correlated with the degree of the deformity and the side of the wedged disc. Cite this article: Bone Joint Res 2014;3:273-9.

Subchondral cyst development and MMP-1 expression during progression of osteoarthritis: an immunohistochemical study.

BACKGROUND: Subchondral bone cyst (SBC) formation is often identified in patients with osteoarthritis. Furthermore, several studies have shown that expression of matrix metalloproteinases (MMPs) is elevated in patients with OA. OBJECTIVES: The aim of our study is to correlate the presence of SBCs and MMP-1 expression with the osteochondral alterations during OA progression. METHODS: We studied the cartilage and subchondral bone of 15 patients who had undergone total knee or hip replacement due to primary OA. As controls, we used the femoral heads of three patients without macroscopic OA changes. We evaluated three specimens per patient. RESULTS: Specimens were divided in four groups based on the Mankin histological severity score. Using immunohistochemistry, we noted SBCs at the site of greatest disease severity. Specifically, these were present more frequently in group III (Mankin score: 6-7) and IV (Mankin: ≥ 8), compared with group I (Mankin: 1-3) and II (Mankin: 4-5). Mild OA stages (Mankin: 1-6) were characterized by degeneration and thinning of the cartilage, followed by increased osteoblast and osteoclast activity of the subjacent bone and the subsequent appearance of SBCs. Simultaneously, we observed expression of MMP-1 in groups I and II in the cartilage and III and IV in both the cartilage and the subchondral bone. Moreover, osteoblast-like cells in the lining of the SBCs showed an increased expression of MMP-1 in stages III and IV. CONCLUSION: Our study provides immunohistological evidence that SBCs accumulate in advanced OA and contain activated cells, which express MMP-1, suggesting that they may thus participate in the osteochondral changes of OA. LEVEL OF EVIDENCE: Level III; prospective comparative study.

Our experience with chemotherapeutic agents in the treatment of breast cancer.

We are reporting about 300 female patients with progressive breast cancer and metastases. One hundred them had been treated by single agent in 5 sub-groups consisting each of 20 patients. Their medial survival was 18.5 month in complete response (CR) patient. One hundred of the patients had 5-drugs chemotherapy with median survival in complete responders of 26 months. One hundred patients had a 5-drug combination chemotherapy including adriblastina with median survival for complete responders of 34 months. In the present work it is apparent that adriblastina prolongs the life of the patients. Our findings and the data of other investigators urge us to consider future experimental pilot protocols which will allow us to individualize treatment by defining for each patient the optimal mix of modalities and agents. We emphasize the use of tumor cell markers and ER receptors.