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Articles by E Kondo
Total Records ( 4 ) for E Kondo
  T Kake , H Kitamura , Y Adachi , T Yoshioka , T Watanabe , H Matsushita , T Fujii , E Kondo , T Tachibe , Y Kawase , K. i Jishage , A Yasoda , M Mukoyama and K. Nakao
 

C-type natriuretic peptide (CNP) plays a critical role in endochondral ossification through guanylyl cyclase-B (GC-B), a natriuretic peptide receptor subtype. Cartilage-specific overexpression of CNP enhances skeletal growth and rescues the dwarfism in a transgenic achondroplasia model with constitutive active mutation of fibroblast growth factor receptor-3. For future clinical application, the efficacy of CNP administration on skeletal growth must be evaluated. Due to the high clearance of CNP, maintaining a high concentration is technically difficult. However, to model high blood CNP concentration, we established a liver-targeted CNP-overexpressing transgenic mouse (SAP-CNP tgm). SAP-CNP tgm exhibited skeletal overgrowth in proportion to the blood CNP concentration and revealed phenotypes of systemic stimulation of cartilage bones, including limbs, paws, costal bones, spine, and skull. Furthermore, in SAP-CNP tgm, the size of the foramen magnum, the insufficient formation of which results in cervico-medullary compression in achondroplasia, also showed significant increase. CNP primarily activates GC-B, but under high concentrations it cross-reacts with guanylyl cyclase-A (GC-A), a natriuretic peptide receptor subtype of atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP). Although activation of GC-A could alter cardiovascular homeostasis, leading to hypotension and heart weight reduction, the skeletal overgrowth phenotype in the line of SAP-CNP tgm with mild overexpression of CNP did not accompany decrease of systolic blood pressure or heart weight. These results suggest that CNP administration stimulates skeletal growth without adverse cardiovascular effect, and thus CNP could be a promising remedy targeting achondroplasia.

  A Yasoda , H Kitamura , T Fujii , E Kondo , N Murao , M Miura , N Kanamoto , Y Komatsu , H Arai and K. Nakao
 

Skeletal dysplasias are a group of genetic disorders characterized by severe impairment of bone growth. Various forms of them add to produce a significant morbidity and mortality, yet no efficient drug therapy has been developed to date. We previously demonstrated that C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, is a potent stimulator of endochondral bone growth. Furthermore, we exhibited that targeted overexpression of a CNP transgene in the growth plate rescued the impaired bone growth observed in a mouse model of achondroplasia (Ach), the most frequent form of human skeletal dysplasias, leading us to propose that CNP may prove to be an effective treatment for this disorder. In the present study, to elucidate whether or not the systemic administration of CNP is a novel drug therapy for skeletal dysplasias, we have investigated the effects of plasma CNP on impaired bone growth in Ach mice that specifically overexpress CNP in the liver under the control of human serum amyloid P component promoter or in those treated with a continuous CNP infusion system. Our results demonstrated that increased plasma CNP from the liver or by iv administration of synthetic CNP-22 rescued the impaired bone growth phenotype of Ach mice without significant adverse effects. These results indicate that treatment with systemic CNP is a potential therapeutic strategy for skeletal dysplasias, including Ach, in humans.

  Y Kobayashi , K Yasuda , E Kondo , T Katsura , Y Tanabe , M Kimura and H. Tohyama
  Background

Concerning meniscal tissue regeneration, many investigators have studied the development of a tissue-engineered meniscus. However, the utility still remains unknown.

Hypothesis

Implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect may significantly enhance fibrocartilage regeneration in vivo in the defect.

Study Design

Controlled laboratory study.

Methods

Seventy-five mature rabbits were used in this study. In each animal, an anterior one-third of the right medial meniscus was resected. Then, the animals were divided into the following 3 groups of 25 rabbits each: In group 1, no treatment was applied to the meniscal defect. In group 2, the defect was covered with a fascia sheath. In group 3, after the resected meniscus was fragmented into small pieces, the fragments were grafted into the defect. Then, the defect with the meniscal fragments was covered with a fascia sheath. In each group, 5 rabbits were used for histological evaluation at 3, 6, and 12 weeks after surgery, and 5 rabbits were used for biomechanical evaluation at 6 and 12 weeks after surgery.

Results

Histologically, large round cells in group 3 were scattered in the core portion of the meniscus-shaped tissue, and the matrix around these cells was positively stained by safranin O and toluisin blue at 12 weeks. The histological score of group 3 was significantly higher than that of group 1 and group 2. Biomechanically, the maximal load and stiffness of group 3 were significantly greater than those of groups 1 and 2.

Conclusion

This study clearly demonstrated that implantation of autogenous meniscal fragments wrapped with a fascia sheath into the donor site meniscal defect significantly enhanced fibrocartilage regeneration in vivo in the defect at 12 weeks after implantation in the rabbit.

Clinical relevance

This study proposed a novel strategy to treat a large defect after a meniscectomy.

  E Kondo , A. M Merican , K Yasuda and A. A. Amis
 

Background: Several trials have compared the clinical results between anatomic double-bundle and single-bundle anterior cruciate ligament reconstruction procedures. However, it remains controversial whether the anatomic double-bundle procedure is superior to the single-bundle procedure.

Hypothesis: The anatomic double-bundle procedure will be better than the single-bundle procedure at resisting anterior laxity, internal rotation laxity, and pivot-shift instability.

Study Design: Controlled laboratory study.

Methods: Eight cadaveric knees were tested in a 6 degrees of freedom rig using the following loading conditions: 90-N anterior tibialforce, 5-N·m internal and external tibial torques, and a simulated pivot-shift test. Tibiofemoral kinematics during the flexion-extension cycle were recorded with an optical tracking system for (1) intact, (2) anterior cruciate ligament–deficient knee, (3) anatomic double-bundle reconstruction, and (4) single-bundle reconstruction placed at 11 o’clock in the intercondylar notch.

Results: There were significant reductions of anterior laxity of 3.5 mm at 20° of flexion, internal rotational laxity of 2.5° at 20° of flexion, and anterior translations (2 mm) and internal rotations (5°) in the simulated pivot-shift test in the double-bundle reconstruction com-pared with the single-bundle reconstruction. There were no significant differences between the 2 procedures for external rotation laxity.

Conclusion: The postoperative anterior translation and internal rotation stability after anatomic double-bundle anterior cruciate ligament reconstruction were significantly better than after single-bundle reconstruction, in both static tests and the pivot shift.

Clinical Relevance: Unlike previous laboratory studies, this work used clinical arthroscopic methods for anterior cruciate ligament reconstruction, and found that the anatomic reconstruction was superior to a single graft placed at 11 o’clock.

 
 
 
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