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- Author: Takashi Saito x
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Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan
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Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan
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Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan
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Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan
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Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan
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Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan
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Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan
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Applied Medical Engineering Science, Graduate School of Medicine, Yamaguchi University, 2-16-1 Tokiwadai, Yamaguchi 755-8611, Japan
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Long-term warfarin use has been reported to increase fracture risk of rib and vertebra but not hip in elderly patients, but the mechanisms remain unknown. We hypothesized that warfarin would impair bone material quality but could not weaken bone strength under conditions with higher mechanical stimuli. To test this hypothesis, rats were randomized to vehicle or warfarin group at 4 weeks of age and subsequently weight matched into a sedentary or jumping exercise group at 12 weeks of age. At 6 months of age, osteocalcin content, bone mineral density (BMD), mineral size, material properties, morphological parameters, and biomechanical properties of cortical bones were evaluated. In order to seek evidence for a common mechanism of action, effects of nucleation rate of mineral crystals on their rigidity were also investigated using computer simulation. In humeral cortical bones, warfarin did not change BMD, but markedly decreased osteocalcin content, diminished mineral size, and impaired material hardness. Consistent with these results, our computer-simulation model showed that osteocalcin-induced delay of mineral crystal nucleation decreased mineral formation rate, increased mean and distribution of mineral sizes, and strengthened mineral rigidity. In tibial cortical bones, warfarin decreased material ultimate stress; however, under jumping exercise, warfarin increased cross-sectional total and bone areas of these tibiae and completely maintained their biomechanical properties including work to failure. Collectively, our findings suggest that long-term warfarin therapy weakens rib and vertebra by impairing cortical bone material quality due to a marked decrease in osteocalcin content but could not reduce hip strength through compensatory adaptation of cortical bone structure to higher mechanical stimuli.
Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Jichi Medical School, Tochigi 329-0498, Japan
Department of Third Internal Medicine, Miyazaki University, Miyazaki 889-1692, Japan
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Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Jichi Medical School, Tochigi 329-0498, Japan
Department of Third Internal Medicine, Miyazaki University, Miyazaki 889-1692, Japan
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Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Jichi Medical School, Tochigi 329-0498, Japan
Department of Third Internal Medicine, Miyazaki University, Miyazaki 889-1692, Japan
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Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Jichi Medical School, Tochigi 329-0498, Japan
Department of Third Internal Medicine, Miyazaki University, Miyazaki 889-1692, Japan
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Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Jichi Medical School, Tochigi 329-0498, Japan
Department of Third Internal Medicine, Miyazaki University, Miyazaki 889-1692, Japan
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Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Jichi Medical School, Tochigi 329-0498, Japan
Department of Third Internal Medicine, Miyazaki University, Miyazaki 889-1692, Japan
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Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Jichi Medical School, Tochigi 329-0498, Japan
Department of Third Internal Medicine, Miyazaki University, Miyazaki 889-1692, Japan
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Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Jichi Medical School, Tochigi 329-0498, Japan
Department of Third Internal Medicine, Miyazaki University, Miyazaki 889-1692, Japan
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Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Jichi Medical School, Tochigi 329-0498, Japan
Department of Third Internal Medicine, Miyazaki University, Miyazaki 889-1692, Japan
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Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Jichi Medical School, Tochigi 329-0498, Japan
Department of Third Internal Medicine, Miyazaki University, Miyazaki 889-1692, Japan
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Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Jichi Medical School, Tochigi 329-0498, Japan
Department of Third Internal Medicine, Miyazaki University, Miyazaki 889-1692, Japan
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We examined the effects of i.c.v. administration of neuro-peptide W-30 (NPW30) on plasma arginine vasopressin (AVP) and plasma oxytocin (OXT) using RIA. The induction of c-fos mRNA, AVP heteronuclear (hn)RNA, and c-Fos protein (Fos) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of rats were also investigated using in situ hybridization histochemistry for c-fos mRNA and AVP hnRNA, and immunohistochemistry for Fos. Both plasma AVP and OXT were significantly increased at 5 and 15 min after i.c.v. administration of NPW30 (2.8 nmol/rat). In situ hybridization histochemistry revealed that the induction of c-fos mRNA and AVP hnRNA in the SON and PVN were significantly increased 15, 30, and 60 min after i.c.v. administration of NPW30 (1.4 nmol/rat). Dual immunostaining for Fos/AVP and Fos/OXT revealed that both AVP-like immunoreactive (LI) cells and OXT-LI cells exhibited nuclear Fos-LI in the SON and PVN, 90 min after i.c.v. administration of NPW30 (2.8 nmol/rat). These results suggest that central NPW30 may be involved in the regulation of secretion of AVP and OXT in the magnocellular neurosecretory cells in the SON and PVN.
