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Biomedical subjects

M Kawata

Publications and source records attributed to M Kawata.

At least 55 records · Page 3Linked to original sources

Slowly progressive heart failure due to subepicardial myocardial fibrosis in a patient with chronic pericardial effusion.

A 65-year-old woman was admitted to hospital because of orthopnea. She had been followed-up for chronic pericardial effusion detected by echocardiography 10 years previously. Initial echocardiography showed that the left ventricular diastolic diameter (LVDd) was 39 mm and percent fractional shortening (%FS) was 33.3%. Neither fluid samples nor a pericardial biopsy specimen identified the etiology. Cardiac tamponade was not evident, and C-reactive protein and creatine-kinase values were within normal limits. During follow-up, the %FS decreased gradually, but the LVDd remained unchanged. On admission, echocardiography showed that the %FS was 12.5% and LVDd was 40 mm. She developed intractable hyponatremic heart failure with bilateral pleural effusion. Autopsy findings revealed that infiltration of small lymphocytes in the epicardium had penetrated into the subepicardial myocardium. The subepicardial myocardium and the interventricular septal myocardium were diffusely replaced by fibrosis, which could have induced restrictive diastolic heart failure and reduced left ventricular contractility. The fibrosis was not detected in the epicardium itself nor the subendocardial myocardium. This is the first report describing diffuse subepicardial myocardial fibrosis in a patient with chronic pericardial effusion and progressive heart failure.

Cardiac Output, Low↗

Expression of prostaglandin E receptor EP4 subtype in rat adrenal zona glomerulosa: involvement in aldosterone release.

We examined the role of prostaglandin (PG) E receptors in the secretion of aldosterone. PGE2 is known to exert its various biological functions by binding to PGE receptors. There are four subtypes of PGE receptors, EP1, EP2, EP3, and EP4. Among the PGE receptors EP2 and EP4 subtypes are coupled to Gs protein and stimulate adenylyl cyclase. In this study, PGE2 caused a dose-dependent increase in aldosterone production from the rat adrenal zona glomerulosa cells in vitro accompanied with an increase in intracellular cAMP concentration. A specific agonist for EP2, butaprost, did not increase the cAMP production or the aldosterone release, suggesting the possibility that EP4 mediates the secretion of aldosterone by PGE2. Northern blot hybridization analysis disclosed that EP4 gene was expressed in the rat adrenal gland but that EP2 gene was not. In situ hybridization revealed that EP4 mRNA is present abundantly in the zona glomerulosa of rat adrenal gland. These findings suggest that the PGE2-EP4 system is involved in the regulation of aldosterone secretion from the rat adrenal gland.

Aldosterone↗

Postnatal development of NADPH-diaphorase activity in the rat: the role of nitric oxide in the ontogeny of arginine vasopression and oxytocin.

To clarify the role of nitric oxide (NO) in the ontogeny of arginine vasopressin (AVP) and oxytocin (OXT) neurons in the hypothalamo-neurohypophysial system (HNS), we observed the coexpression pattern of NADPH-diaphorase (NADPH-d) activity and AVP- or OXT-immunoreactivity (IR) in the rat hypothalamus and posterior pituitary during the postnatal period. The enzymatic activity of NADPH-d was observed in the supraoptic nucleus (SON), paraventricular nucleus (PVN), median eminence (ME) and posterior pituitary throughout the postnatal development. AVP-containing neurons were clearly observed from postnatal day 1 in both the SON and PVN, while OXT-containing neurons were recognized from postnatal day 14. The coexistence of NADPH-d and AVP or OXT was detected in the SON from postnatal day 14. At postnatal day 21, the coexpression pattern was approximately the same as that of the SON and PVN in adult rats. Our findings indicated that the expression of NADPH-d and OXT was observed from almost the same postnatal period in both the SON and PVN. In addition, the pattern of increased numbers of NADPH-d positive fibers was similar to that of OXT-immunoreactive fibers in both the inner layer of the ME and the posterior pituitary. A good correlation was thus obtained between OXT expression and NADPH-d activity in the HNS during postnatal development. The present study suggests that NO is more closely involved in the expression and regulation of secretion of OXT than AVP.

Animals↗

[Diffuse left ventricular hypokinesis mimicking dilated cardiomyopathy with multi-vessel coronary vasospasm].

We investigated 7 patients with multi-vessel coronary vasospasm (> or = 75%) and diffuse left ventricular hypokinesis by coronary angiography and echocardiography. Four patients were male and 3 were female and mean +/- SD age was 63.0 +/- 11.2 years. Chief complaints were dyspnea in 3 patients, and chest pain, appetite loss, palpitation and general fatigue in one each. New York Heart Association functional classification was I in one patient, II in 5 and III in one. Mean heart rate was 73.9 +/- 11.6 beats/min. Initial echocardiography showed left ventricular end-diastolic diameter (LVDd) 54.4 +/- 5.5 mm, left ventricular end-systolic diameter (LVDs) 43.7 +/- 4.8 mm and percentage fractional shortening (%FS) 19.7 +/- 2.6%. The left ventricle was not remarkably enlarged despite poor contraction. Coronary vasospasm was induced after acetylcholine injection into the right coronary artery in 6 patients, left anterior descending artery in 7 and circumflex artery in 5. Four patients developed three-vessel coronary vasospasm. Three patients underwent endomyocardial biopsy which showed non-specific mild fibrosis. They were treated with nitrates and/or Ca-antagonists to prevent coronary vasospasm. Follow-up echocardiography was performed in 6 patients after 8.5 +/- 6.6 months. Echocardiography revealed marked improvement in left ventricular contraction (LVDd 49.7 +/- 4.6 mm, LVDs 35.8 +/- 4.4 mm, p < 0.05; %FS 27.9 +/- 4.5%, p < 0.05). These data suggested that left ventricular dilation was not prominent despite the poor contractility in patients with multi-vessel coronary vasospasm and diffuse left ventricular hypokinesis. The left ventricular dysfunction might be hibernating myocardium produced by multiple episodes of coronary vasospasm. Anti-vasospastic agents were effective in these patients.

Acetylcholine↗

[Corticosteroid receptor and stress].

Adrenal corticosteroids readily enter the brain and exert markedly diverse effects, such as stress response of the target neural cells. These effects are regulated via two receptor systems, the mineralocorticoid receptor (MR; type I corticosteroid receptor) and the glucocorticoid receptor (GR; type II corticosteroid receptor), both of which are ligand-dependent transcription factors. MR is localized mainly in the hippocampus, and GR is distributed throughout the brain. MR and GR, however, are highly colocalized in the hippocampus, which is a target of the stress hormone and an especially plastic and vulnerable region of the brain. MR has a high affinity for corticosterone/cortisol, a common endogenous ligand for MR and GR, and is extensively bound at low levels of circulating corticosterone/cortisol. GR has a lower affinity and is extensively bound at high levels of circulating corticosterone/cortisol. These findings suggest that MR plays major roles under physiological conditions, whereas GR is mainly effective at high concentrations of corticosterone/cortisol, such as stressful conditions. The interactions of MR and GR in the hippocampal regions could be important for regulating stress response in the brain.

Animals↗

Protein kinase C lies on the signaling pathway for vascular endothelial growth factor-mediated tumor development and angiogenesis.

The growth of any solid tumor depends on angiogenesis. Among the known angiogenic factors, vascular endothelial growth factor (VEGF) has been shown to play a pivotal role in tumor angiogenesis. However, to date, the signal transduction pathway initiated by VEGF is still not fully understood. It has been suggested that protein kinase C (PKC) plays an important role in the VEGF-induced signal transduction pathway in vitro, although the role of PKC in tumor angiogenesis in vivo still remains to be elucidated. By delivering the VEGF gene within the self-contained tetracycline-regulated retroviral vector (Retro-Tet) into hepatocellular carcinoma (HCC) cells, we manipulated VEGF expression by providing tetracycline in the drinking water to assess the tumor kinetics mediated exclusively by VEGF. In this study, we combined this Retro-tet system and LY333531, an inhibitor of the PKC-beta isoform, to elucidate the role of PKC-beta in tumor development and angiogenesis. Using a syngenic xenograft model, tumor augmentation induced by VEGF overexpression in HCC was markedly suppressed by oral administration of the PKC-beta inhibitor, with an accompanying reduction of neovascularization and p44/42 mitogen-activated protein kinase activation. This inhibitory effect was achieved even after the tumor was fully established. Immunohistochemical analysis revealed that apoptosis increased markedly in the tumor upon PKC-beta inhibitor treatment, whereas tumor cell proliferation itself did not change. Furthermore, with orthotopical transplantation, PKC-beta inhibition suppressed HCC tumor development in the liver. These results suggest that PKC-beta lies on the signal transduction pathway by which VEGF augments development and angiogenesis not only at the initial stage but also after the tumor is fully established.

Animals↗

Down-regulation of ACTH and glucocorticoid receptor immunoreactivity in hypothalamic arcuate neurons after adrenalectomy in the rat.

The expression of glucocorticoid receptor (GR) in rat adrenocorticotropin (ACTH)-containing neurons in rat brain was immunohistochemically investigated. ACTH-containing cell bodies were found mainly in the arcuate nucleus. Most of these neurons exhibited GR immunoreactivities in their nuclei. ACTH-containing nerve fibers were distributed in the bed nucleus of the stria terminalis, periventricular nucleus, retrochiasmatic nucleus, parvocellular part of paraventricular nucleus and dorsomedial hypothalamic nucleus. After adrenalectomy there was a marked decrease of ACTH immunoreactivity, as well as GR immunoreactivity, in neurons of the arcuate nucleus, but ACTH immunoreactivity in the fibers was not affected. These results indicate that glucocorticoids up-regulate ACTH and GR production in hypothalamic arcuate neurons, but that glucocorticoid-induced changes could be delayed in the fibers derived from these neurons.

Adrenal Glands↗

KDR/Flk-1 is a major regulator of vascular endothelial growth factor-induced tumor development and angiogenesis in murine hepatocellular carcinoma cells.

Vascular endothelial growth factor (VEGF), which is one of the most potent angiogenic factors, has been shown to play a pivotal role in tumor angiogenesis, including hepatocellular carcinoma (HCC). The effects of VEGF are mediated mainly through two distinct receptors, flt-1 and KDR/Flk-1. It has been suggested that KDR/Flk-1 plays an important role in tumor development. However, the role of KDR/Flk-1 in HCC has not been examined. We previously reported that VEGF tightly regulated murine HCC development, based on the results of a study using a retroviral tetracycline-regulated (Retro-Tet) gene expression system. This system allows VEGF gene expression to be manipulated in vivo by providing tetracycline in the drinking water. In the present study, we combined the KDR/Flk-1-specific neutralizing monoclonal antibody (KDR/Flk-1mAb) and the Retro-Tet system to elucidate the role of KDR/Flk-1 in VEGF-induced tumor development and angiogenesis in a murine HCC experimental model. In a xenograft study, tumor augmentation induced by VEGF overexpression was almost abolished by means of KDR/Flk-1mAb treatment, with accompanying inhibition of angiogenesis, KDR/Flk-1 autophosphorylation, but not interference of flt-1 activation. This inhibitory effect was achieved even on established tumors and regardless of whether the tumor size was small or large. On the contrary, KDR/Flk-1mAb treatment significantly increased the apoptosis in the tumor. With orthotopic transplantation, KDR/Flk-1mAb also inhibited HCC development in the liver. These results suggest that KDR/Flk-1 is a major regulator of VEGF-mediated HCC development and angiogenesis not only at the initial stage, but also after the tumor has fully developed.

Animals↗

Changes in serotonergic neurons in the brain of pyrithiamine-induced acute thiamine-deficient mice.

We examined changes in 5-hydroxytriptamine (5-HT, serotonin) neurons in pyrithiamine-induced thiamine deficiency in mice immunohistochemically. Extensive decreases in the densities of 5-HT-immunoreactive fibers were detected in the lateral septal nucleus, the thalamus, the medial mammillary nucleus, the dorsal and the median raphe nuclei, the raphe obscurus nucleus, the tegmental area, the cerebellum and the vestibular nucleus, though only a small decrease was detected in the inferior colliculus. Most remarkably, degenerative winding fibers were detected between the deep mesencephalic nucleus and the ventral tegmental area. Increases in intensity of 5-HT immunoreactivity in the dorsal raphe nucleus and decreases in the number of 5-HT-immunoreactive cell bodies in the dorsal and the median raphe nuclei were detected. These results demonstrated the differential vulnerability of 5-HT neurons in thiamine-deficient mice. This is the first report to demonstrate changes in 5-HT neurons immunohistochemically throughout the brain of pyrithiamine-induced thiamine deficient mouse.

Animals↗

Cellular localization and distribution of glucocorticoid receptor immunoreactivity and the expression of glucocorticoid receptor messenger RNA in rat pituitary gland. A combined double immunohistochemistry study and in situ hybridization histochemical analysis.

By means of double immunohistochemical techniques and a nonradioisotopic in situ hybridization method, we determined the colocalization pattern of glucocorticoid receptor (GR) and pituitary hormones and the GR messenger RNA (mRNA) expression in the pituitaries of Wistar adult male rats. Immunoreactivity for GR was detected in the nuclei of cells in the anterior and posterior pituitary. Double immunohistochemistry revealed that the colocalization of GR and anterior pituitary hormones occurred in almost 99% of the growth hormone (GH)-producing cells and adrenocorticotropic hormone (ACTH)-producing cells, and in 67% of the thyroid stimulating hormone (TSH)-producing cells. Almost all of the folliculostellate cells (93%), marginal layer cells (94%) in the anterior pituitary, and pituicytes (96%) in the posterior pituitary immunostained for S100 protein antibody were also immunostained with GR. GR mRNA was abundant in the cytoplasm of anterior and intermediate pituitary cells but scattered sparsely in that of the posterior pituitary. These results suggest that glucocorticoids directly influence certain pituitary cells in order to regulate cell function, including the synthesis and/or secretion of hormones.

Animals↗

A method of tracking donor cells after simulated autologous transplantation: a study using synovial cells of transgenic rats.

A transgenic rat was used as a transplantation donor to simulate autologous transplantation. The sex-matched transplantation between a female transgenic and a wild-type rat can theoretically be regarded as an autologous transplantation due to the genetic agreement of these rats except for the non-protein-producing transgenes. Transgene-containing synovial cells were tracked in the joint using this autologous transplantation model. The transgenes in the donor synovial cells were detected using in situ hybridization (ISH), while mitotic activities were simultaneously examined by immunodetection of 5-bromo-2'-deoxyuridine (BrdU). A defect was generated in the knee joint capsule of a Fischer 344 (wild-type) rat. The synovium of a transgenic rat was sutured to the defect of the wild-type rat in group 1 and was allowed to free float in the joint in group 2. A large number of BrdU-labeled, transgene-containing synovial cells were detected in both groups at 3 days. The number of these cells then decreased, but they could still be identified even at 4 weeks after autologous transplantation. These results indicated that transplanted synovial cells were viable in the joint for at least 4 weeks. Furthermore, the transgenic rat was shown to be an effective animal model for distinguishing the extrinsic from the intrinsic cells in the cellular intermixed tissues in vivo. The combined method of ISH for detecting transgene-containing cells and the immunohistochemistry of BrdU for detecting proliferating cells was also shown to be effective for tracking the viability of extrinsic cells after autologous transplantation.

Animals↗

Long-term lack of endogenous glucocorticoids down-regulates glucocorticoid receptor levels in the rat forebrain.

To understand the effect of a chronic lack of endogenous glucocorticoids on glucocorticoid receptor levels, the changes of glucocorticoid receptor content in the rat forebrain five months after adrenalectomy were investigated. In the long-term adrenalectomized rats that showed a hormone deficiency and loss of glucocorticoid receptor immunoreactivity in the forebrain, an intraperitoneal injection of corticosterone was used to elevate the serum hormone levels and recover glucocorticoid receptor immunoreactivity in the forebrain. One hour later, when the blood corticosterone returned to the normal level, the recovery of glucocorticoid receptor immunoreactivity in the forebrain was examined by immunohistochemistry. Since the complete restoration of glucocorticoid receptor immunoreactivity was shown to depend on the presence of normal levels of both serum hormone and intracellular glucocorticoid receptors, the weak reappearance of glucocorticoid receptor immunoreactivity in any forebrain area of the long-term adrenalectomized rats that had normal serum corticosterone might reflect the low intracellular glucocorticoid receptor levels there. Our results revealed a weak reappearance of glucocorticoid receptor immunoreactivity in some forebrain areas of the long-term adrenalectomized rats after corticosterone treatment; the hippocampal granule cell layer and cerebral cortex in particular showed very weak recovery of glucocorticoid receptor immunoreactivity. Conversely, neurons in the CA1/CA2 subfields of the hippocampal pyramidal cell layer, immediately adjacent to the granule cell layer on the same brain section, exhibited a strong reappearance of glucocorticoid receptor immunoreactivity, to near normal levels. These results suggest that, five months after adrenalectomy, the intracellular glucocorticoid receptor content decreased in the rat granule cell layer and cerebral cortex. Therefore, the long-term lack of endogenous glucocorticoids after adrenalectomy might down-regulate but not up-regulate the intracellular glucocorticoid receptor level, and the presence of glucocorticoids is important for the continued synthesis of glucocorticoid receptors.

Adrenalectomy↗

Distribution of glucocorticoid receptor immunoreactivity in gastric mucosa of normal and adrenalectomized rats.

Glucocorticoids have many effects in the stomach. It is well known that glucocorticoids function via the glucocorticoid receptor (GR). In this study, GR immunoreactivity in the gastric mucosa of normal and adrenalectomized (ADX) rats was examined immunohistochemically by using specific polyclonal antibodies against rat GR. In the gastric mucosa of normal rats, GR immunoreactivity was observed in the nuclei of morphologically identified parietal cells. Double immunohistochemical staining for GR and parietal cell, anti-parietal cell antibody-positive cells also had positive immunoreactions for GR. In the gastric mucosa of ADX rats, GR immunoreactivity was diminished in the nuclei of parietal cells but weak immunoreactivity was still observed. These results suggest that parietal cells in the gastric mucosa of rats are directly regulated by glucocorticoids via its receptors. Nuclear GR immunoreactivity in gastric parietal cells is thought to depend on the circulating ligands.

Adrenalectomy↗

Real-time imaging of glucocorticoid receptor dynamics in living neurons and glial cells in comparison with non-neural cells.

To investigate the intracellular trafficking of glucocorticoid receptor (GR) in response to various conditions in a single living cell, a green fluorescent protein (GFP) and rat GR chimera construct (GFP-GR) was prepared. We transiently transfected GFP-GR into primary cultured rat hippocampal neurons, cortical glial cells, and non-neural cells, e.g. COS-1 cells and CV-1 cells, and compared the dynamic changes in subcellular localization of GFP-GR in these cells. When GFP-GR was expressed in the cells, GFP-GR efficiently transactivated the mouse mammary tumour virus promoter in response to dexamethasone (DEX). The cytoplasm-to-nuclear translocation of GFP-GR induced with 10(-7) m DEX, a specific agonist of GR, at 37 degrees C was completed within 30 min in all cell types used, and the rate of nuclear translocation was dependent on the ligand dose. The translocation of GFP-GR into the nucleus from the cytoplasm was induced in a ligand-specific manner, similar to that of the native GR. The disruption of microtubules by colchicine or nocodazole showed no significant effect on the DEX-induced GFP-GR translocation from the cytoplasmic region to the nuclear region. The cells were not deteriorated during time-lapse imaging analysis for 1 h at 37 degrees C. The present findings suggest that the subcellular localization of GFP-GR is dynamically changed in response to extracellular and intracellular conditions, and that there are no conspicuous variations in the manner of trafficking of GR among different types of cells in vitro.

Animals↗

Catecholamine release from isolated guinea pig lungs during sympathetic stimulation with varied ventilation and perfusion.

This study was performed to elucidate catecholamine release in the pulmonary circulation of isolated lungs due to the sympathetic nerve stimulation and to assess the experimental conditions which can modify the release, i.e., stimulus intensity, ventilation state of the lung and flow rate of perfusion. In artificially ventilated lungs, electrical stimulation of stellate ganglions evoked large noradrenaline efflux from the lung, but adrenaline efflux was below the detection limit, and dopamine was not detected in any case. In the unventilated preparations, the lung parenchyma were not bleached and the arterial pressure was significantly higher than in ventilated preparations. Noradrenaline efflux from the unventilated group was significantly lower than that from the ventilated preparations. The effect of the perfusion flow rate was investigated under pressure-operated ventilation. The pulmonary arterial pressure (Pa) was not varied at 5-10 ml min-1, but it was increased significantly at 20 ml min-1. Noradrenaline efflux was also increased significantly at 20 ml min-1. These results indicate that noradrenaline was the catecholamine exclusively released from pulmonary vasculature due to the sympathetic nerve stimulation, and that both ventilation and the perfusion flow rate could affect the release. The concomitant increase in arterial pressure indicates that noradrenaline efflux would be affected by the alteration in resistive small arteries. Circulatory change in these arteries is supposed to be one of the factors that modify noradrenaline release from the lungs. The analysis of noradrenaline should be a useful method to evaluate the sympathetic effect on the pulmonary vasculature.

Animals↗

Immunocytochemical analysis of sex differences in calcitonin gene-related peptide in the rat dorsal root ganglion, with special reference to estrogen and its receptor.

Previous studies have shown that the calcitonin gene-related peptide (CGRP) immunoreactivity in the central nervous system (CNS) of adult rats is sexually dimorphic and regulated by sex steroid. In the present study, we used immunocytochemistry to investigate the sex difference in CGRP-immunoreactive (IR) neurons in rat dorsal root ganglia (DRG). The numbers of CGRP-IR neurons at the cervical, lumbar and sacral levels in the female rats were significantly lower than those of the male rats. We also found that the number of CGRP-IR neurons at the lumbar level was increased in ovariectomized (OVX) rats, but was decreased in estradiol (E2)-treated rats (OVX+E2). A large number of estrogen receptor (ER)-IR neurons at the lumbar level were found in the female rats, and its number was greater than that in the male rats. We also investigated the change in the number of ER-IR neurons of OVX rats after estrogen treatment. The number of ER-IR neurons in the OVX+E2 rats was consistent with that of the intact female rats, but was significantly increased in the OVX rats. As shown by a double-labeling immunocytochemical method, over 80% of the CGRP-IR neurons at the lumbar level showed ER immunoreactivity in the female, OVX and OVX+E2 rats, compared to only about 46% in the male rats. These results indicate that there is a gender difference in CGRP expression in the rat DRG, and that this CGRP expression might be downregulated by estrogen (at least in part) through its receptor.

Animals↗

Metabolic labeling of a subset of glial cells by UDP-galactose: implication for astrocyte lineage diversity.

Astrocytes are implicated in many aspects of brain function; however, it remains unclear whether astrocytes arise from a single cell lineage. It is therefore important to obtain new markers for the astrocyte cell lineage. We show that exogenously added UDP-galactose (UDP-Gal) can be used to metabolically label a subset of glial fibrillary acidic protein-positive (GFAP+) cells. UDP-Gal was incorporated into the cultured embryonic mouse brain slices in a time-dependent manner. Surprisingly, the transferred sugar moiety was no longer Gal but was mainly glucose. Most of the radioactivity was transferred to a polymer of glucose, most likely to be glycogen, and also to glucosyl ceramide. In the slice culture, the reaction products were distributed densely in the ventricular zone and also on process-like structures extending to the pial surface. In dissociation culture, UDP-Gal labeled some of the GFAP+ cells and some of the vimentin+ cells. Because radial glial cells (RGCs) contain glycogen and change from vimentin+ to GFAP+, it is strongly suggested that UDP-Gal labeled RGCs and their descendants. Only 27% of the GFAP+ cells were labeled with UDP-Gal, which suggests that only a subset of astrocytes are derived from RGCs and that there is a discrete group of GFAP+ cells that is not generated from RGCs.

Animals↗

Role of chondroitin sulfate-hyaluronan interactions in the viscoelastic properties of extracellular matrices and fluids.

The purpose of this study was to investigate the role of chondroitin sulfate-hyaluronan interactions in the viscoelastic properties of tissues and fluids, using capillary and cone-on-plate viscometers. Chondroitin sulfate markedly increased the viscosity of hyaluronan solutions at a wide range of hyaluronan mass (50-1900 kDa) under physiological conditions of pH, temperature, ionic strength and glycosaminoglycan concentration (0.5-40 mg/ml), although the viscosity of the chondroitin sulfate solutions themselves was very low. In the assay using a cone-on-plate viscometer, chondroitin sulfate increased the viscosity of hyaluronan solutions at various shear rates. At low shear rates, the viscosity of a chondroitin sulfate (5 mg/ml)-hyaluronan (0.5 mg/ml) mixture was about 40% of that of an aggrecan (5 mg/ml)-hyaluronan (0.5 mg/ml) mixture, and at 2.8-fold higher concentrations, chondroitin sulfate elicited the same effect on the viscosity of hyaluronan solutions (5 mg/ml) as an aggrecan monomer. In the presence of oscillatory motion, the addition of aggrecan increased the elasticity (storage) modulus G' and the viscosity (loss) modulus G" of hyaluronan solutions and markedly decreased the loss tangent G"/G' at frequencies corresponding to normal joint movements. In contrast, chondroitin sulfate had only a marginal effect on the loss tangent G"/G', although it increased G' and G". These findings demonstrated that chondroitin sulfate, as well as aggrecan, increases the viscosity of hyaluronan solutions, although chondroitin sulfate has less effect on the elasticity of hyaluronan solutions than that of aggrecan, and suggest that chondroitin sulfate may play an important physiological role in determining the viscoelastic properties of extracellular matrices and fluids.

Aggrecans↗