Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability.

OBJECTIVE: Prevalence of ankle osteoarthritis (OA) is lower than that of knee OA, however, the molecular mechanisms underlying the difference remain unrevealed. In the present study, we developed mouse ankle OA models for use as tools to investigate pathophysiology of ankle OA and molecular characteristics of ankle cartilage. DESIGN: We anatomically and histologically examined ankle and knee joints of C57BL/6 mice, and compared them with human samples. We examined joints of 8-week-old and 25-month-old mice. For experimental models, we developed three different ankle OA models: a medial model, a lateral model, and a bilateral model, by resection of respective structures. OA severity was evaluated 8 weeks after the surgery by safranin O staining, and cartilage degradation in the medial model was sequentially examined. RESULTS: Anatomical and histological features of human and mouse ankle joints were comparable. Additionally, the mouse ankle joint was more resistant to cartilage degeneration with aging than the mouse knee joint. In the medial model, the tibiotalar joint was markedly affected while the subtalar joint was less degenerated. In the lateral model, the subtalar joint was mainly affected while the tibiotalar joint was less altered. In the bilateral model, both joints were markedly degenerated. In the time course of the medial model, TdT-mediated dUTP nick end labeling (TUNEL) staining and Adamts5 expression were enhanced at early and middle stages, while Mmp13 expression was gradually increased during the OA development. CONCLUSION: Since human and mouse ankles are comparable, the present models will contribute to ankle OA pathophysiology and general cartilage research in future.

Electric-field control of ferromagnetism.

It is often assumed that it is not possible to alter the properties of magnetic materials once they have been prepared and put into use. For example, although magnetic materials are used in information technology to store trillions of bits (in the form of magnetization directions established by applying external magnetic fields), the properties of the magnetic medium itself remain unchanged on magnetization reversal. The ability to externally control the properties of magnetic materials would be highly desirable from fundamental and technological viewpoints, particularly in view of recent developments in magnetoelectronics and spintronics. In semiconductors, the conductivity can be varied by applying an electric field, but the electrical manipulation of magnetism has proved elusive. Here we demonstrate electric-field control of ferromagnetism in a thin-film semiconducting alloy, using an insulating-gate field-effect transistor structure. By applying electric fields, we are able to vary isothermally and reversibly the transition temperature of hole-induced ferromagnetism.

The angiotensin I-converting enzyme inhibitor, cilazapril inhibits the platelet-derived growth factor B chain expression in glomeruli of spontaneously hypertensive rats.

To clarify whether in vivo expression of growth factors in the glomerulus is induced in a hypertensive animal model, we investigated the expression of platelet-derived growth factor (PDGF) B chain, transforming growth factor beta (TGF-beta), and angiotensin II (Ang II) type 1 receptors in glomeruli of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. We also investigated the effects of treatment with cilazapril, and angiotensin I-converting enzyme inhibitor, on this expression. First, the expression of PDGF B chain, TGF-beta, and Ang II receptors from the glomerulus were investigated using the reverse-transcriptase polymerase chain reaction in SHR and WKY rats. Although there was no significant difference in PDGF B chain, TGF-beta, and Ang II receptors from the glomerulus were investigated using the reverse-transcriptase polymerase chain reaction in SHR and WKY rats. Although there was no significant difference in PDGF B chain, TGF-beta or Ang II receptor expression between SHR and WKY rats at the age of 7 weeks, the PDGF B chain expression of 16-week-old SHR was significantly higher (4.4-fold) than that of age-matched WKY rats. Next, we administered oral cilazapril at a dose of 10 mg/kg to 13-week-old SHR daily for 3 weeks. The systolic blood pressure in SHR treated with cilazapril was significantly lower than that in control SHR. After administration of cilazapril for 3 weeks, we examined the in vivo expression of growth factors and Ang II receptors in the glomerulus. The PDGF B chain expression was suppressed by treatment with cilazapril (2.5-fold) as compared with nontreated SHR. No alteration in TGF-beta or Ang II receptor expression was detected. We did not find any histological changes in the kidneys of SHR, WKY rats or cilazapril-treated SHR, and cilazapril treatment did not suppress the glomerular size. These findings indicate that the expression of PDGF B chain in the glomerulus preceded the appearance of histological changes in SHR and that the administration of cilazapril inhibited the expression of PDGF B chain without affecting the glomerular size. This suggests that angiotensin I-converting enzyme inhibitors directly suppress the Ang II-induced PDGF B chain promotion in the glomerulus of SHR at the established hypertensive stage.

Angiotensin II induces in vivo c-fos expression from rat renal cortex and medulla.

In order to verify whether angiotensin II (Ang II) induced in vivo protooncogene, c-fos, expression in the rat renal cortex and medulla, we administered various concentrations of Ang II to Wistar rats and measured the c-fos expression from the renal cortex and medulla using the method of Northern hybridization. c-fos expression induced by 1 microgram (1.6 x 10(-6) M) of atrial natriuretic peptide (ANP) was also examined. The result was that the peak expression of c-fos mRNA was observed at approximately 10 min after Ang II administration in both rat renal cortex and medulla. This expression was reduced to the control level at 30 min. The measurement of the concentration of injected-Ang II and c-fos mRNA expression revealed that the peak expression of c-fos mRNA in the renal cortex and medulla was detected at the concentration of 1.0 x 10(-8) M and 1.0 x 10(-9) M Ang II, respectively. Nevertheless, ANP had no significant effect on the increase in c-fos mRNA expression. These data revealed that Ang II transiently increases the in vivo c-fos expression in both rat renal cortex and medulla but ANP does not. This protooncogene expression may induce vascular and mesangial proliferation in the kidney.

Alteration of renal receptors for atrial natriuretic peptide and vasopressin in spontaneously hypertensive rats treated with antihypertensive diuretics.

To investigate the alteration of the renal atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) receptors in the controlled hypertensive state of spontaneously hypertensive rat (SHR) treated with antihypertensive diuretics, 12 weeks old SHRs were administered an antihypertensive diuretic, furosemide, trichloromethiazide, or indapamide, daily for 10 days and investigated by radiolabeled receptor assay (RRA) of ANP and AVP. The urine volume was significantly increased in all groups treated with antihypertensive diuretics as compared with the untreated control group on day 3. Systolic blood pressure was significantly decreased in groups treated with both trichloromethiazide and indapamide. The number of renal ANP receptors decreased; affinity was increased only in the SHR administered indapamide. The affinity of the renal AVP receptor was also decreased in that group. Alteration of ANP and AVP receptors was observed only in the group treated with indapamide. This indicates that the ANP and AVP receptor in the kidney of SHR was changed not only by diuresis or reduction of blood pressure, but by the pharmacological action of indapamide.