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Estradiol is an estrogen steroid hormone and is produced basically within the follicles of the ovaries. The decrease in serum estrogens concentration at menopause disrupts the metabolic balance, changes the lipid profile leading to visceral obesity, which caused an increase in serum estradiol levels, through aromatase activity. Estrogen deficiency also is a reason for the development of osteoporosis.We investigated the serum estradiol levels and changes in bone alpha estrogen receptor expression in ovariectomized rats. For this purpose, we used 20 female Wistar rats at reproductive age - 2 months divided into 2 groups: group 1 (G1)-10 animals were ovariectomized and group 2 (G2)-10 of which were sham-operated. All animals of G1 showed weight gain compared to group G2. The results showed that the values of serum 17β-estradiol in rats of G1 statistically increased compared to G2 (p

Introduction. Canonical Wnt signaling pathway regulates stromal stem cells (SSCs) differentiation and controls the balance between adipogenesis and osteogenesis. Estrogen deficiency affects Wnt signaling by altering the expression of sclerostin (SCL) and the peroxisome proliferator-activated receptor-∝ coactivator 1-∝(PGC-1∝) in the bone tissue. The objective of the study was to monitor whether there is a feedback mechanism between SCL and PGC-1∝ and to determine the extent of the immunohistochemical staining of PGC-1∝ and SCL in bone tissue of estrogen deficiency-induced osteoporosis in female Wistar rats. Materials and methods. An experiment was performed on 20 female Wistar rats at reproductive age (2 months), divided into 2 groups: in group 1 (G1) 10 animals were ovariectomized (ovx) and in group 2 (G2) 10 of the remaining were sham-operated (sham). Results. We found that the PGC-1∝ in the bone marrow stromal cells was reduced in the group with osteoporosis (G1 – ovariectomized rats), compared to sham-operated control group G2 (p

Application of safe-by-design approach for curing osteoporosis – a lock at the future

Purpose: Hemodynamic stress in arterial hypertension leading to increased production of endothelin-1 (ET-1). Changes in the extracellular matrix are controlled largely by methalloproteinase-2 (MMP-2) and methalloproteinase-9 (MMP-9) which play an important role in vascular remodeling of hypertension. C-reactive protein (CRP) is an acute phase protein which is synthesized by hepatocytes under the effect of interleukin-6 (IL-6) in inflammation. The purpose of the study was to investigate the relationship of ET-1, MMP-2, MMP-9 and CRP with the degree of arterial hypertension and the systemic and vascular inflammatory response. Methods: Three groups were formed: group I - 31 patients with mild hypertension (MH); group II - 29 patients with severe hypertension (SH); group III - 15 persons in a control group (CG). ET-1 was determined by ELISA kit of "Biomedika", MMP-2 and MMP-9 by ELISA kit of the "R&D Systems", and the CRP- through immunoturbidimetric method with monoclonal anti-CRP antibodies. The analysis used the statistical program STATGRAPHICS. Results: It was found that there was a statistically significant difference between serum concentration of ET-1 (pg/ml) at MH when compared to CG (p = 0.0189) and SH compared to CG (p = 0.0181). There is a statistically significant difference between concentration of MMP-9 (ng/ml) of SH when compared to CG (p = 0.0010) and between MH when compared to SH (p = 0.0006). There is no statistically significant difference of MMP-2 (ng/ml) between the three groups (p> 0.05). There is also a statistically significant difference between the concentrations of CRP (mg/l) at MH when compared with CG (p = 0.0170) and SH when compared with CG (p = 0.0366). Conclusions: Serum levels of ET-1 are increased in the groups with arterial hypertension, which demonstrates its role in the pathogenesis of the disease. The levels of MMP-9 are greatly reduced in patients with severe hypertension which can be used as an indicator of increased cardiovascular risk in these patients. Serum levels of MMP-2 do not show specific changes at the different degrees of hypertension. Based on our experimental data can be concluded that the levels of MMP-9 in arterial hypertension are defined by complex causes - the degree of hypertension, drug therapy and accompanying cardiovascular diseases and complications. The average levels of CRP at MH and SH are significantly increased which confirms the pathogenetic relationship of arterial hypertension with systemic and vascular inflammation.

Purpose: Matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9) are representatives of the group of gelatinases that have similar effect, resulting in the degradation of collagen type IV. MMP-2 and MMP-9 have a key role in the pathogenesis of atherosclerosis. The aim of the present study was to determine the extent of the immunohistochemical expression of MMP-2 and MMP-9 in the vascular wall of the abdominal aorta in patients with atherosclerotic changes. Methods: We investigated by immunohistochemistry (polyclonal antibodies,class IgG, Santa Cruz Biotechnology, USA) the expressional changes of MMP-2 and MMP-9 in abdominal aorta obtained from autopsied cases. We used 5 nonatherosclerotic (control group - G1) and 20 atherosclerotic segments (group - G2) from human abdominal aorta. These arteries were colected at autopsy from 25 cases within 5 hours of death. Results: In the nonatherosclerotic aorta MMP-2 and MMP-9 were expressed mainly in the endothelium and the smooth muscle cells (VSMC) of the vascular wall. The expression of MMP-2 and MMP-9 was significantly increased (p