The effect of estrogens and dietary calcium deficiency on the extracellular matrix of articular cartilage in Göttingen miniature pigs
Clinical observations have suggested that estrogens are involved in the pathogenesis of postmenopausal osteoarthritis (OA). However, positive and negative associations between the incidence of OA and serum estrogen concentrations have been reported. In contrast to this, osteoporosis is regarded as a disease with a strong estrogen-dependent component. Moreover, there is an interaction between estrogen and calcium deficiency: calcium supplementation potentiates the effect of estrogen therapy. The present study was designed to investigate how estrogen deficiency affects the articular cartilage depending on calcium supply. The distribution of different types of glycosaminoglycans and collagens can be used as an indicator for extracellular matrix changes induced by estrogen deficiency. Different levels of dietary calcium were therefore fed to intact and ovariectomized Göttingen miniature pigs for one year before articular cartilage was harvested. The histochemical staining for heavy sulfated glycosaminoglycans in the extracellular matrix of ovariectomized miniature pigs, especially of those fed with a low calcium diet, was stronger in comparison to intact animals. In intact animals type II-collagen was immunodetected in all zones of unmineralized and mineralized articular cartilage, while immunostaining for this protein was negative to weak in the deep radiated fiber zone of ovariectomized minipigs. These results suggest that the synthesis of heavy sulfated glycosaminoglycans and immunohistochemically detectable type II-collagen is possibly influenced by estrogen deficiency. In conclusion, under estrogen deficiency, the extracellular matrix of articular cartilage underwent similar changes to those observed in physiologically aging cartilage where keratan sulfate is increased as a heavy sulfated glycosaminoglycan.
Available from: Peter Van Overschee
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ABSTRACT: In this paper, we generalize a class of existing linear subspace identification techniques to subspace identification algorithms for bilinear, discrete time, time invariant systems. A major assumption we make is that the input should be white. It is shown that in that case most of the properties of linear subspace identification theory can be extended to equivalent properties for bilinear systems. The practical interest of the method is illustrated by applying it to a model of a distillation column. Key Words : Subspace identification, Bilinear Kalman filtering 1 Introduction Industrial processes are very often controlled on the basis of linear models ( if a model is used at all !). When a process is stable and operating around a small region of a fixed working point one can indeed assume that it can be approximated by a linear system. In many industrial applications however, especially chemical industry, processes are strongly nonlinear and the operating point may change considerabl...
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ABSTRACT: Vascular endothelial growth factor (VEGF) has been recently shown to play an important role during endochondral bone formation in hypertrophic cartilage remodeling, ossification, and angiogenesis. To our knowledge there are no previous studies investigating the role of VEGF in osteoporosis. We hypothesized that VEGF expression in bone would be reduced under glucocorticoid (GC) treatment and tested this in a minipig model. As part of a larger study, 17 primiparous sows (Göttingen minipig) were allocated to two experimental groups when they were 15 months old: a control group (n = 9) and a group receiving GC treatment for 15 months (n = 8). All animals were fed a semisynthetic diet until they were sacrificed. The GC group received prednisolone orally at a daily dose of 1 mg/kg body wt for 8 weeks and thereafter 0.5 mg/kg body wt. VEGF levels in lumbar vertebrae were measured by enzyme-linked immunosorbent assay (ELISA) and verified by Western blot analysis. VEGF and its receptors (VEGFR) were localized by immunohistochemistry. Expression of VEGF-mRNA was analyzed by reverse transcription-polymerase chain reaction. VEGF protein was quantified in supernatants of cultivated osteoblasts by ELISA. Spinal bone mineral density was assessed in vivo by quantitative computed tomography. Expression of cyclooxygenase-2 (COX-2) protein was investigated by immunohistochemistry. High VEGF concentrations were measured in normal lumbar vertebrae whereas VEGF concentrations were 60% lower (P < 0.0001) in GC-treated minipigs. VEGF levels were associated (r = 0.7) with rates of spinal trabecular bone loss, which differed significantly (P < 0.0013) between controls (-0.47 +/- 2.2% SEM) and GC-treated minipigs (-12.8 +/- 2.3% SEM). Osteoblasts were immunopositive for VEGF. VEGF receptors VEGFR-2 (KDR, flk-1) and VEGFR-1 (flt-1) could be immunostained on osteoclasts and osteoblasts. VEGF-mRNA and protein were detectable in the lumbar vertebrae of all animals. The expression of COX-2 protein was decreased in GC-treated animals. VEGF is produced in osteoblasts and its concentration is decreased in GC-treated animals as well as in osteoblasts exposed to GC. Since reductions in VEGF concentrations correlate with parallel measurement of bone mineral density in GC-treated minipigs we hypothesize that VEGF may be an important modulating factor for bone remodeling, specifically in GC-induced osteoporosis. GC inhibit COX-2 and hence prostaglandin E2 (PGE2) production. Since PGE2 is able to increase VEGF synthesis, this may be the link between GC and VEGF decrease.
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ABSTRACT: Osteoarthritis and osteoporosis are two major health problems affecting more than 60% of post-menopausal women in the United States. The promotion of healthy aging and the prevention and reduction of morbidity and mortality is a main concern for healthcare providers. The similarities and differences in pathophysiology, diagnosis, and treatment for osteoarthritis and osteoporosis are often not clear for clinicians. Some osteoporosis treatments, including bisphosphonates and vitamin D, seem to have a beneficial effect on osteoarthritis as well. A review of these two conditions in terms of bone mineral density, bone turnover, hormonal effects, and treatment options will be discussed.
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