All issues
Volume 34 (2013)
- Issue 6 Pages 275-
- Issue 5 Pages 215-
- Issue 4 Pages 173-
- Issue 3 Pages 119-
- Issue 2 Pages 61-
- Issue 1 Pages 1-
Volume 34, Issue 3
June
Displaying 1-7 of 7 articles from this issue
- |<
- <
- 1
- >
- >|
Full Papers
-
Taku KOJIMA, Tomoka HASEGAWA, Paulo Henrique Luiz DE FREITAS, Tomomaya ...2013 Volume 34 Issue 3 Pages 119-128
Published: 2013
Released on J-STAGE: June 19, 2013
JOURNAL FREE ACCESSWe have histologically examined vascular invasion and calcification of the hypertrophic zone during endochondral ossification in matrix metalloproteinase (MMP)-9 deficient (MMP-9-/-) mice and in their littermates at 3 days, 3 weeks and 6 weeks after birth. Capillaries and osteoclasts at the chondro-osseous junction showed an intense MMP-9 immunopositivity, suggesting that they recognize chemical properties of cartilaginous matrices, and then release MMP-9 for cartilage degradation. CD31-positive capillaries and tartrate-resistant acid phosphatase-reactive osteoclasts could be found in the close proximity in the region of chondro-osseous junction in MMP-9-/- mice, while in wild-type mice, vascular invasion preceded osteoclastic migration into the epiphyseal cartilage. Although MMP-9-/- mice revealed larger hypertrophic zones, the index of calcified area was significantly smaller in MMP-9-/- mice. Interestingly, the lower layer of the MMP-9-/- hypertrophic zone showed intense MMP-13 staining, which could not be observed in wild-type mice. This indicates that MMP-13 may compensate for MMP-9 deficiency at that specific region, but not to a point at which the deficiency could be completely rescued. In conclusion, it seems that MMP-9 is the optimal enzyme for cartilage degradation during endochondral ossification by controlling vascular invasion and subsequent osteoclastic migration.View full abstractDownload PDF (1574K) -
Kazuto YAMAZAKI, Takaki KAGAYA, Misako WATANABE, Hiroki TERAUCHI, Dais ...2013 Volume 34 Issue 3 Pages 129-136
Published: 2013
Released on J-STAGE: June 19, 2013
JOURNAL FREE ACCESSGlucagon-like peptide 2 (GLP-2) is an intestinotropic peptide that binds to GLP-2 receptor (GLP-2R), a class-B G protein-coupled receptor. The GLP-2R antagonist GLP-2(3-33) has relatively high partial agonistic activity, and there are as yet no ideal known potent GLP-2R antagonists. We therefore prepared several truncated forms of human GLP-2 and characterized them by binding and reporter assays to find antagonists more potent than GLP-2(3-33). We found that GLP-2(11-33) was the most potent orthosteric GLP-2R antagonist, with binding activity almost equal to those of GLP-2 and GLP-2(3-33) and weaker intrinsic agonistic activity than GLP-2(3-33). GLP-2(11-33) retained weak agonistic activity toward human, cynomolgus monkey, dog, and Syrian hamster GLP-2Rs. However, it had no agonistic activity toward rat GLP-2R. GLP-2(11-33) potentiated the agonistic activity of an ago-allosteric modulator of GLP-2R, compound 1 (N-[1-(2,5-dichlorothiophen-3-yl)-2-(phenylsulfanyl)ethylidene]hydroxylamine), synergistically toward human GLP-2R. In the case of rat GLP-2R, GLP-2(11-33) decreased the agonistic activity of compound 1, although GLP-2 and GLP-2(3-33) increased this activity additively. These findings suggest that the binding sites of the ago-allosteric modulator and GLP-2 overlap, at least in rat GLP-2R. GLP-2(11-33) is a novel, useful tool for analyzing the mode of action of agonists and ago-allosteric modulators of GLP-2R.View full abstractDownload PDF (450K) -
Toyohito SEGAWA, Naohisa MIYAKOSHI, Yuji KASUKAWA, Hiroshi AONUMA, Hi ...2013 Volume 34 Issue 3 Pages 137-141
Published: 2013
Released on J-STAGE: June 19, 2013
JOURNAL FREE ACCESSMinodronate is expected to produce greater analgesic effects than other bisphosphonates. However, there are no studies comparing bisphosphonate analgesic effects on formalin-induced acute inflammatory pain in rats. The purpose of the present study was to evaluate the analgesic effects of minodronate, morphine, and placebo. Four-month-old female Wistar rats were administered minodronate (50 mg/kg), morphine (10 mg/kg), or vehicle (n = 10 each) injections. Thirty minutes later, all rats were injected with formalin (right hind paw) to induce acute inflammatory pain. Paw licking and lifting as indicators of nociceptive pain responses were monitored from 0 to 5 min (phase 1; chemical-stimulation state) and then from 10 to 30 min (phase 2; spinal-sensitized state) after injection. The percentage of limb usage of the formalin-injected and the non-injected sides were measured in phases 1 and 2 by counting foot stamps. Minodronate significantly decreased nociceptive responses and increased limb usage compared with vehicle in phase 2 only (P < 0.05). Morphine significantly decreased nociceptive responses and increased limb usage compared with minodronate and vehicle in both phase 1 and 2 (P < 0.05). In conclusion, minodronate showed significant analgesic effects for formalin-induced acute pain in the spinal-sensitized state.View full abstractDownload PDF (3249K) -
Naoki OGANE, Masanori YASUDA, Yoichi KAMEDA, Tomoyuki YOKOSE, Hisamori ...2013 Volume 34 Issue 3 Pages 143-151
Published: 2013
Released on J-STAGE: June 19, 2013
JOURNAL FREE ACCESSPaclitaxel and carboplatin (TC) chemotherapy is an effective and well-tolerated regimen against advanced endometrial cancer. Organic anion transporting polypeptide 1B3 (OATP1B3) and copper transporter 1 (CTR1) are critical for the uptake of paclitaxel and carboplatin, respectively. This study aimed to address the prognostic impact of OATP1B3 and CTR1 in endometrial cancer patients treated with adjuvant TC chemotherapy. We immunohistochemically evaluated the expressions of OATP1B3 and CTR1 in 47 stage III endometrial cancers. The high expression levels of OATP1B3 were significantly correlated with type I tumor (P = 0.0005). In univariate analysis, high expression levels of OATP1B3 (P = 0.047) and CTR1 (P = 0.009) were significantly associated with longer disease-free survival (DFS) and longer overall survival (OS), respectively. The patients with tumors showing high expression levels of at least one of OATP1B3 and CTR1 had potentially longer DFS (P = 0.058) and significantly longer OS (P = 0.003) sin the univariate analysis. Combined OATP1B3/CTR1 expression was the sole independent prognostic factor for longer OS in the multivariate analysis (P = 0.013). Our findings suggest that combined OATP1B3/CTR1 expression is a possible predictive/prognostic factor for a good outcome in stage III endometrial cancer patients treated with adjuvant TC chemotherapy.View full abstractDownload PDF (6348K) -
Tomoka HASEGAWA, Norio AMIZUKA, Tamaki YAMADA, Zhusheng LIU, Yukina MI ...2013 Volume 34 Issue 3 Pages 153-159
Published: 2013
Released on J-STAGE: June 19, 2013
JOURNAL FREE ACCESSSclerostin, an osteocyte-derived molecule, has been reported to serve as a negative regulator of osteoblastic activity as well as bone remodeling. However, there is no report that verified the regional difference for sclerostin synthesis, and in this study we have investigated immunolocalization of sclerostin by comparing dentin matrix protein (DMP) 1, an osteocyte-derived factor broadly expressed in tibial metaphyses and cortical bone. In metaphyseal primary trabecules, a site of bone modeling, strong DMP1-reactivity was observed in osteocytic lacunar-canalicular system (OLCS), while faint staining for sclerostin was visible only in a few osteocytes. In secondary trabecules, in which bone remodeling begins, some osteocytes showed intense sclerostin-immunopositivity, though there were many DMP1-positive osteocytes. In cortical bone, there were more osteocytes reactive for sclerostin, when compared with those in the secondary trabecules. Silver impregnation verified that immature, primary trabecules contained randomly-oriented OLCS, while mature, cortical bone showed geometrically well-arrangement of OLCS. Taken together, though DMP1 is broadly synthesized in bone, sclerostin appears to be abundantly synthesized in regular OLCS of cortical bone, but less produced in irregular OLCS as seen in primary trabecules, indicating the regional difference for sclerostin synthesis.View full abstractDownload PDF (1091K) -
Naokatu ARAKAKI, Arisa YAMASHITA, Shingo NIIMI, Tetsuo YAMAZAKI2013 Volume 34 Issue 3 Pages 161-166
Published: 2013
Released on J-STAGE: June 19, 2013
JOURNAL FREE ACCESSBone remodeling is regulated by local factors that regulate bone-forming osteoblasts and boneresorbing osteoclasts, in addition to hormonal activity. Recent studies have shown that reactive oxygen species (ROS) act as an intracellular signal mediator for osteoclast differentiation. However the role of ROS on osteoblast differentiation is poorly understood. Here, we investigated the impact of ROS on osteoblastic differentiation of MC3T3-E1 cells. Osteogenic induction resulted in notable enhancement of mineralization and expression of osteogenic marker gene alkaline phosphatase, which were accompanied by an increase in ROS production. Additionally, we found that mitochondrial morphology dynamically changed from tubular reticulum to fragmented structures during the differentiation, suggesting that mitochondrial morphological transition is a novel osteoblast differentiation index. The antioxidant N-acetyl cysteine prevented not only ROS production but also mineralization and mitochondrial fragmentation. It is therefore suggested that the ROSdependent signaling pathways play a role in osteoblast differentiation accompanied by mitochondrial morphological transition.View full abstractDownload PDF (898K)
Communication
-
Fengjuan LI, Yoko TAKAHASHI, Kohji YAMAKI2013 Volume 34 Issue 3 Pages 167-171
Published: 2013
Released on J-STAGE: June 19, 2013
JOURNAL FREE ACCESSRenin is a crucial enzyme in the renin-angiotensin system, and the inhibition of its activity is considered as a useful approach to the treatment of hypertension. The inhibitory effect of catechinrelated compounds on renin was investigated in this work. It was found that epigallocatechin gallate (EGCg) possessed the strongest activity with an IC50 value of 44.53 μM and acted in an un ompetitive manner. Gallated catechins exerted higher inhibition than the ungallated forms, and gallic acid exhibited an inhibitory potency close to that of epicatechin gallate (ECg). Results indicated that the galloyl moiety and ortho-trihydroxy phenyl structures might be favorable for the renin-inhibitory activity of these compounds.View full abstractDownload PDF (325K)
- |<
- <
- 1
- >
- >|