elastin and Osteoporosis

Vascular calcification occurred as the last step of arteriosclerosis makes a lot of disturbances on vascular function and should influence on the worsening of the vascular diseases. Calcium is the main component of the vascular calcification like bone, and one of causes of vascular calcification should be the hypoparathyroidism due to the lowering of serum calcium and the following calcium paradox seen in osteoporosis. Bone calcium must shift to the arterial wall from the bone. Medial calcification could be formed under the molecular regulatory control like in bone by differentiated osteoblast or chondroblast from pericyte like cell origin smooth muscle cell. Many substances such as osteopontine, osteocalcine, bone morphogenetic protein 2, matrix Gla protein and alkaliphosphatase were found in calcified area. In intimal calcification, degenerated elastin and macrophage originated calcification were found. In the process of degeneration of elastin polypentapeptide structure in elastin can be easily conbined to Ca(2+), elastin-Ca(2+) complex is neutralized by PO4(2-) and calcium phosphate is accumulated in degenerated elastin.

Topics: Alkaline Phosphatase; Aortic Diseases; Arteriosclerosis; Bone Morphogenetic Protein 2; Calcinosis; Calcium; Calcium-Binding Proteins; Elastin; Extracellular Matrix Proteins; Humans; Hypoparathyroidism; Macrophages; Matrix Gla Protein; Osteocalcin; Osteopontin; Osteoporosis

Topics: Animals; Cattle; Chick Embryo; Collagen; Connective Tissue; Elastin; Glucocorticoids; Growth Disorders; Humans; In Vitro Techniques; Osteoporosis; Vitamin A

Osteoporosis is a common bone disease that results in elevated risk of fracture, and delayed bone healing and impaired bone regeneration are implicated by this disease. In this study, Elastin/Polycaprolactone/nHA nanofibrous scaffold in combination with mesenchymal stem cells were used to regenerate bone defects. Cytotoxicity, cytocompatibility and cellular morphology were evaluated in vitro and observations revealed that an appropriate environment for cellular attachment, growth, migration, and proliferation is provided by this scaffold. At 3 months following ovariectomy (OVX), the rats were used as animal models with an induced critical size defect in the femur to evaluate the therapeutic potential of osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) seeded on 3 dimension (3D) scaffolds. In this experimental study, 24 female Wistar rats were equally divided into three groups: Control, scaffold (non-seeded BM-MSC), and scaffold + cell (seeded BM-MSC) groups. 30 days after surgery, the right femur was removed, and underwent a stereological analysis and RNA extraction in order to examine the expression of Bmp-2 and Vegf genes. The results showed a significant increase in stereological parameters and expression of Bmp-2 and Vegf in scaffold and scaffold + cell groups compared to the control rats. The present study suggests that the use of the 3D Elastin/Polycaprolactone (PCL)/Nano hydroxyapatite (nHA) scaffold in combination with MSCs may improve the fracture regeneration and accelerates bone healing at the osteotomy site in rats.

Topics: Animals; Biocompatible Materials; Cell Differentiation; Cell Survival; Durapatite; Elastin; Female; Materials Testing; Mesenchymal Stem Cells; Microscopy, Electron, Scanning; Nanostructures; Osteogenesis; Osteoporosis; Polyesters; Rats; Rats, Wistar; Tissue Engineering; Tissue Scaffolds

Many epidemiological studies have reported that the severity of arterial diseases such as arterial calcification and stiffness is inversely related to bone loss, i.e., osteoporosis. However, the nature of this relationship is unclear. The purpose of the present study was to examine the influences of estrogen deficiency and/or low-calcium diet (0.1% Ca) on bone metabolism and calcium balance, as well as aortic wall composition and stiffness in young female rats. Twenty-eight 6-week-old female rats were randomized into four groups: OVX-Low calcium (OL) and OVX-Normal calcium groups (ON) were ovariectomized, and Sham-Low calcium (SL) and Sham-Normal calcium groups (SN) were sham-operated. After 12 weeks, the bone mineral density of the lumbar spine and tibial proximal metaphysis were significantly lower in ON than in SN, and also significantly lower in OL than in ON. Additionally, OL rats had significant higher (vs. SN and SL) urinary deoxypyridinoline, but not urinary calcium, excretion at 4 weeks after ovariectomy. However, at 12 weeks after ovariectomy, urinary calcium excretion was significantly higher in OL than in SL, with corresponding increases in two bone turnover markers, bone-type alkaline phosphatase and tartrate-resistant acid phosphatase. Neither estrogen deficiency nor low-calcium diet affected aortic stiffness or elastin degeneration and calcium deposition over the course of the present study, although changes of bone metabolism occurred rapidly. Taken together, these results show that bone loss and arterial stiffness did not progress simultaneously in the present experimental protocol.

Topics: Animals; Aortic Diseases; Bone Density; Calcium; Calcium, Dietary; Elastin; Estrogens; Female; Osteoporosis; Ovariectomy; Random Allocation; Rats; Rats, Sprague-Dawley

The effects of estrogen replacement therapy in menopausal women are more obvious on bones than on the cardiovascular system. The optimal estrogen dosage may differ in these different parts of the body. In hypertensive rats, low doses have been shown to reduce arterial collagen and stiffness, whereas higher dosages are required for osteoprotection. From 4 to 20 weeks of age, female spontaneously hypertensive rats (SHRs) were divided into four groups: without ovariectomy, under placebo or 17 beta-estradiol (10 micrograms/kg/day), and with ovariectomy under either placebo or 17 beta-estradiol (same dosage). Serial tail systolic blood pressure measurements were performed, and histomorphometry of the thoracic aorta was determined at the end of the study. Under estrogen, blood pressure was unchanged, whereas the aortic wall-to-lumen ratio was increased, particularly in the presence of ovariectomy. The elastin to collagen ratio was significantly decreased, due both to a decrease in elastin and an increase in collagen density, with no change in media thickness. The latter findings were not observed when ovariectomy was performed. Independent of changes in wall stress, high-dose estrogen increases the aortic extracellular matrix in female SHRs. This increase may be reversed in the presence of ovariectomy, suggesting that estrogen was not the only gonadal factor responsible for altered vascular structure and function.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Elastin; Estradiol; Extracellular Matrix; Female; Hemodynamics; Hormone Replacement Therapy; Myocardium; Osteoporosis; Ovariectomy; Rats; Rats, Inbred SHR