Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

<p>Abstract</p> <p>Background</p> <p>Periprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin) deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in <it>Calca </it>-/- mice.</p> <p>Methods</p> <p>We used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10 C57BL/6J wild-type (WT) mice and twenty <it>Calca </it>-/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles (Group 2), <it>Calca </it>-/- mice without UHMWPE particles (Group 3), <it>Calca </it>-/- mice with UHMWPE particles (Group 4), <it>Calca </it>-/- mice without UHMWPE particles and calcitonin substitution (Group 5), and <it>Calca </it>-/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6). Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP) + cells.</p> <p>Results</p> <p>Bone resorption was significantly increased in <it>Calca </it>-/- mice compared with their corresponding WT. The eroded surface in <it>Calca </it>-/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in <it>Calca </it>-/- mice after particle implantation. Serum OPG (osteoprotegerin) increased significantly after CT substitution.</p> <p>Conclusions</p> <p>As anticipated, <it>Calca </it>-/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.</p

Mechanisms leading to increased vasodilator responses to calcitonin-gene-related peptide in mesenteric resistance arteries of early pregnant rats.

Contains fulltext : 69189.pdf (publisher's version ) (Closed access)The objective of this study was to explore the mechanism responsible for the higher relaxing responses of mesenteric arteries to calcitonin-gene-related peptide (CGRP) in pregnancy. We performed myograph and ligand binding studies to determine the role of matrix metalloproteinase-2 (MMP-2) and CGRP receptor density. MMP activity was manipulated in isolated arteries by exposing them to the blocking effects of doxycycline. Vascular activity of MMP-2 was studied by gelatin zymography, and CGRP receptor density was determined by ligand binding analysis. Compared to nonpregnant rats, CGRP elicited stronger arterial relaxation in pregnant rats. The latter effect was neither accompanied by a change in relaxing responses to direct activation of adenylyl cyclase by forskolin nor by a change in the response to stimulation of G-protein-coupled adrenergic receptors by isoproterenol. Doxycycline did not affect the stronger arterial relaxation in pregnancy in spite of the observed more than threefold higher arterial MMP-2 activity. Density of binding sites for [(125)I]CGRP in arteries from pregnant rats (64 +/- 14 fmol/mg protein) and from virgin rats (54 +/- 5 fmol/mg protein) were comparable. The results of this study provide evidence for increased coupling of CGRP receptors to adenylyl cyclase in early pregnancy

Pregnancy enhances the prejunctional vasodilator response to adrenomedullin in selective regions of the arterial bed of Wistar rats.

Contains fulltext : 52225.pdf (publisher's version ) (Closed access)The objective of this study is to determine whether the vascular response to adrenomedullin is modulated by pregnancy. To this end, the authors study the effect of adrenomedullin on different contractile responses of mesenteric, uterine, renal, and saphenous arteries of 10-day pregnant and nonpregnant rats in myographs. Adrenomedullin inhibited contractile responses induced by electrical field stimulation in only the mesenteric and uterine arteries. This effect was more pronounced during pregnancy than in the nonpregnant state. Adrenomedullin did not modify concentration response curves to noradrenaline. The reduction of contractile responses to 40 mmol/L K(+) by adrenomedullin was similar in arteries of pregnant and nonpregnant rats. However, after incubation with capsaicin, this effect was significantly increased in mesenteric arteries of the pregnant group. The authors conclude that pregnancy is associated with a rise in the prejunctional inhibitory effect of adrenomedullin in some regions of the arterial system