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Kozo Nakamura

Publications and source records attributed to Kozo Nakamura.

At least 91 records · Page 5Linked to original sources

Synergistic effects of FGF-2 with insulin or IGF-I on the proliferation of human auricular chondrocytes.

Chondrocyte preparation with the safety and efficiency is the first step in cartilage regenerative medicine. To prepare a chondrocyte proliferation medium that does not contain fetal bovine serum (FBS) and that provides more than a 1000-fold increase in cell numbers within approximately 1 month, we attempted to use the medium containing 5% human serum (HS), but it exerted no more than twofold increase in 2 weeks. To compensate for the limited proliferation ability in HS, we investigated the combinational effects of 12 factors [i.e., fibroblast growth factor (FGF)-2, insulin-like growth factor (IGF)-I, insulin, bone morphogenetic protein-2, parathyroid hormone, growth hormone, dexamethasone, 1alpha25-dihydroxy vitamin D3, L-3,3',5'-triodothyronine, interleukine-1 receptor antagonist, 17beta-estradiol, and testosterone] on the proliferation of human auricular chondrocytes by analysis of variance in fractional factorial design. As a result, FGF-2, dexamethasone, insulin, and IGF-I possessed promotional effects on proliferation, while the combination of FGF-2 with insulin or IGF-I synergistically enhanced the proliferation. Actually, the chondrocytes increased 7.5-fold in number in 2 weeks in a medium containing 5% HS with 10 ng/ml FGF-2, while the cell number synergistically gained a 10-12-fold increase with 5 microg/ml insulin or 100 ng/ml IGF-I in the same period. The proliferation effects were more enhanced at a concentration of 100 ng/ml for FGF-2, and especially for the combination of 100 ng/ml FGF-2 and 5 microg/ml insulin (approximately 16-fold within 2 weeks). In the long-term culture with repeated passaging, this combination provided more than 10,000-fold within 8 weeks (i.e., passage 4). Thus, we concluded that such a combination of FGF-2 with insulin or IGF-I may be useful for promotion of auricular chondrocyte proliferation in a clinical application for cartilage regeneration.

Adolescent↗

Alveolar bone marrow as a cell source for regenerative medicine: differences between alveolar and iliac bone marrow stromal cells.

UNLABELLED: We isolated and expanded BMSCs from human alveolar/jaw bone at a high success rate (70%). These cells had potent osteogenic potential in vitro and in vivo, although their chondrogenic and adipogenic potential was less than that of iliac cells. INTRODUCTION: Human bone marrow stromal cells (BMSCs) have osteogenic, chondrogenic, and adipogenic potential, but marrow aspiration from iliac crest is an invasive procedure. Alveolar BMSCs may be more useful for regenerative medicine, because the marrow can be aspirated from alveolar bone with minimal pain. MATERIALS AND METHODS: In this study, alveolar bone marrow samples were obtained from 41 patients, 6-66 years of age, during the course of oral surgery. BMSCs were seeded and maintained in culture with 10% FBS and basic fibroblast growth factor. In addition, BMSCs were induced to differentiate into osteoblasts, chondrocytes, or adipocytes in appropriate medium. RESULTS AND CONCLUSION: From a small volume (0.1-3 ml) of aspirates, alveolar BMSCs expanded at a success ratio of 29/41 (70%). The success rate decreased with increasing donor age, perhaps because of age-dependent decreases in the number and proliferative capacity of BMSCs. The expanded BMSCs differentiated into osteoblasts under osteogenic conditions in 21-28 days: the mRNA levels of osteocalcin, osteopontin, and bone sialoprotein, along with the calcium level, in alveolar BMSC cultures were similar to those in iliac cultures. However, unlike iliac BMSC, alveolar BMSC showed poor chondrogenic or adipogenic potential, and similar differences were observed between canine alveolar and iliac BMSCs. Subsequently, human alveolar BMSCs attached to beta-tricalcium phosphate were transplanted into immunodeficient mice. In transplants, new bone formed with osteoblasts and osteocytes that expressed human vimentin, human osteocalcin, and human GAPDH. These findings suggest that BMSCs have distinctive features depending on their in vivo location and that alveolar BMSCs will be useful in cell therapy for bone diseases.

Adipocytes↗

Surgical treatment for atlantoaxial subluxation with myelopathy in spondyloepiphyseal dysplasia congenita.

STUDY DESIGN: A retrospective review of 21 patients with spondyloepiphyseal dysplasia congenita (SEDC), including 7 operated patients for atlantoaxial subluxation. OBJECTIVES: To clarify the morphological findings of atlantoaxial subluxation in SEDC patients and to evaluate the operative procedures based on these image findings. SUMMARY AND BACKGROUND DATA: The presence of atlanto axial sublucation with hypoplasia of the odontoid and/or lax ligaments leads to myelopathy in patients with spondyloepiphyseal dysplasia congenita. METHODS: We retropectively reviewed the physical and morphological findings on atlantoaxial images and the clinical findings of myelopathy in 21 patients with SEDC. RESULTS: Myelopathy was found in 9 individuals with severe SEDC who presented with marked short stature and severe coxa vara; of these, 6 had gait disturbances. On the images of the 9 patients with myelopathy, the average sagittal canal diameter (SCD) at the level of the atlas was only 9.2 mm (range, 7-12 mm) with progressive atlantoaxial subluxation. The average atlantodental interval (ADI) was 3.5 mm (range, 2-6 mm) in the presence of a sagittal atlas diameter (SAD) of less than 27.1 mm (range, 22-36 mm). Surgery was performed for 6 of the patients with myelopathy. Since their SADs were small, and the average SCD, at 9.9 mm (8-14 mm), was narrow even at the position of extension (the position of reduction for atlantoaxial subluxation), C1 laminectomy was needed for all these patients, and occipital-cervical posterior fusion was performed. Stability was satisfactory in all cases and the operative outcome for myelopathy was excellent for 1 case, fine for 4, and fair for 2. CONCLUSION: A small SAD may limit the effectiveness of reducing atlantoaxial subluxation. Persistent narrowing of the SCD may require concomitant C1 laminectomy and occipital-cervical fusion.

Adolescent↗

Supramolecular nanocarrier of siRNA from PEG-based block catiomer carrying diamine side chain with distinctive pKa directed to enhance intracellular gene silencing.

An siRNA nanocarrier formed through self-assembly of PEG-based block catiomer possessing two distinct amino groups with different pKa values in a side chain was developed. This design provided the carrier with a sufficient siRNA complexation and an assumed buffering capacity in the endosomes, allowing it to exhibit remarkable gene knockdown abilities as well as sufficient serum tolerability.

Cations↗

Surface grafting of artificial joints with a biocompatible polymer for preventing periprosthetic osteolysis.

Periprosthetic osteolysis-bone loss in the vicinity of a prosthesis-is the most serious problem limiting the longevity of artificial joints. It is caused by bone-resorptive responses to wear particles originating from the articulating surface. This study investigated the effects of graft polymerization of our original biocompatible phospholipid polymer 2-methacryloyloxyethyl phosphorylcholine (MPC) onto the polyethylene surface. Mechanical studies using a hip-joint simulator revealed that the MPC grafting markedly decreased the friction and the amount of wear. Osteoclastic bone resorption induced by subperiosteal injection of particles onto mouse calvariae was abolished by the MPC grafting on particles. MPC-grafted particles were shown to be biologically inert by culture systems with respect to phagocytosis and resorptive cytokine secretion by macrophages, subsequent expression of receptor activator of NF-kappaB ligand in osteoblasts, and osteoclastogenesis from bone marrow cells. From the mechanical and biological advantages, we believe that our approach will make a major improvement in artificial joints by preventing periprosthetic osteolysis.

Biocompatible Materials↗

Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes.

The Komeda miniature rat Ishikawa (KMI) is a naturally occurring mutant caused by an autosomal recessive mutation mri, which exhibits longitudinal growth retardation. Here we identified the mri mutation as a deletion in the rat gene encoding cGMP-dependent protein kinase type II (cGKII). KMIs showed an expanded growth plate and impaired bone healing with abnormal accumulation of postmitotic but nonhypertrophic chondrocytes. Ex vivo culture of KMI chondrocytes reproduced the differentiation impairment, which was restored by introducing the adenovirus-mediated cGKII gene. The expression of Sox9, an inhibitory regulator of hypertrophic differentiation, persisted in the nuclei of postmitotic chondrocytes of the KMI growth plate. Transfection experiments in culture systems revealed that cGKII attenuated the Sox9 functions to induce the chondrogenic differentiation and to inhibit the hypertrophic differentiation of chondrocytes. This attenuation of Sox9 was due to the cGKII inhibition of nuclear entry of Sox9. The impaired differentiation of cultured KMI chondrocytes was restored by the silencing of Sox9 through RNA interference. Hence, the present study for the first time shed light on a novel role of cGKII as a molecular switch, coupling the cessation of proliferation and the start of hypertrophic differentiation of chondrocytes through attenuation of Sox9 function.

Animals↗

The nuchal ligament restrains cervical spine flexion.

STUDY DESIGN: A biomechanical study using a cadaver model was conducted to define the function of the nuchal ligament in the restraint of flexion of the cervical spine. OBJECTIVE: To test the hypothesis that surgical resection of the nuchal ligament significantly reduces the structural restraints to cervical flexion. SUMMARY OF BACKGROUND DATA: Although previous studies have examined the role of the posterior ligaments and capsules on cervical stability, no prior study has quantified the biomechanical significance of the nuchal ligament. The clinical significance may include progressive loss of lordosis or even kyphosis after trauma or posterior surgical procedures such as laminectomy, laminoplasty, or tumor resection. METHODS: Cervical spines from the occiput to the first thoracic vertebra were harvested from 12 human cadavers. Specimens were tested under 3 conditions: all ligaments intact, after resection of the nuchal ligament, and then after additional resection of the supraspinous, interspinous, and yellow ligaments. Flexion moments were applied; load and displacement were measured. Changes in flexion range of motion and tangent stiffness between treatment conditions were statistically compared. RESULTS: The flexion range increased 28% after removing the nuchal ligament. After subsequent resections, the flexion range increased 52% compared with intact (P <0.005). Tangent stiffness decreased 27% after nuchal ligament resection; after all resections, stiffness was 35% lower than intact (P <0.05). CONCLUSION: Resection of the nuchal ligament increased the flexion range of motion and decreased stiffness in flexion. Injury to the nuchal ligament may increase the risk of cervical spine instability and malalignment.

Aged↗

Spatial relations between the vertebral body and the thoracic aorta in adolescent idiopathic scoliosis.

STUDY DESIGN: An analysis of computed tomography images of patients with adolescent idiopathic scoliosis. OBJECTIVES: To evaluate the spatial relations between the vertebral body and the thoracic aorta and to verify the safety of anterior instrumentation surgery. SUMMARY OF BACKGROUND DATA: Recent studies have suggested that the aorta is positioned more laterally and posteriorly in patients with idiopathic scoliosis than in normal patients; however, no study used rib heads as references in the analysis. METHODS: Computed tomography images of the whole thoracic spine of 10 patients with adolescent idiopathic scoliosis were analyzed. A line that passed the anterior edge of the bilateral rib heads was regarded as the virtual passage of the screw used for anterior instrumentation surgery. Whether this line crossed the aorta was investigated. A distance between the vertebral body and the aorta was measured along this line. RESULTS: The aorta was located more posteriorly between T6 and T9. At these levels, the virtual passage of the screw crossed the aorta in 33 of 40 vertebrae (83%). At seven vertebrae in 5 patients, this passage crossed the aorta and the distance was less than 2 mm. Of these, four were T6, two T7, and one T8. CONCLUSION: In some patients with adolescent idiopathic scoliosis, the aorta can be located in the direction of the screw passage and close to the vertebral body. Accordingly, when planning anterior instrumentation surgery for right thoracic curve, surgeons should pay attention to these spatial relations.

Adolescent↗

Analysis of phenolic compounds in white rice, brown rice, and germinated brown rice.

Two hydroxycinnamate sucrose esters, 6'-O-(E)-feruloylsucrose and 6'-O-(E)-sinapoylsucrose, were isolated from methanol extracts of rice bran. Soluble and insoluble phenolic compounds as well as 6'-O-(E)-feruloylsucrose and 6'-O-(E)-sinapoylsucrose from white rice, brown rice, and germinated brown rice were analyzed using HPLC. The results demonstrated that the content of insoluble phenolic compounds was significantly higher than that of soluble phenolics in rice, whereas almost all compounds identified in germinated brown rice and brown rice were more abundant than those in white rice. 6'-O-(E)-Feruloylsucrose (1.09 mg/100 g of flour) and 6'-O-(E)-sinapoylsucrose (0.41 mg/100 g of flour) were found to be the major soluble phenolic compounds in brown rice. During germination, an approximately 70% decrease was observed in the content of the two hydroxycinnamate sucrose esters, whereas free phenolic acid content increased significantly; the ferulic acid content of brown rice (0.32 mg/100 g of flour) increased to 0.48 mg/100 g of flour and became the most abundant phenolic compound in germinated brown rice. The content of sinapinic acid increased to 0.21 mg/100 g of flour, which is nearly 10 times as much as that in brown rice (0.02 mg/100 g of flour). In addition, the total content of insoluble phenolic compounds increased from 18.47 mg/100 g of flour in brown rice to 24.78 mg/100 g of flour in germinated brown rice. These data suggest that appropriate germination of brown rice may be a method to improve health-related benefits.

Chromatography, High Pressure Liquid↗

Opposing extracellular signal-regulated kinase and Akt pathways control Schwann cell myelination.

Schwann cells are the myelinating glia of the peripheral nervous system, and their development is regulated by various growth factors, such as neuregulin, platelet-derived growth factor (PDGF), and insulin-like growth factor-I (IGF-I). However, the mechanism of intracellular signaling pathways following these ligand stimuli in Schwann cell differentiation remains elusive. Here, we demonstrate that in cultured Schwann cells, neuregulin and PDGF suppressed the expression of myelin-associated protein markers, whereas IGF-I promoted it. Although these ligands activated common downstream signaling pathways [i.e., extracellular signal-regulated kinase (Erk) and phosphatidylinositol-3-kinase (PI3K)-Akt pathways], the profiles of activation varied among ligands. To elucidate the function of these pathways and the mechanisms underlying Schwann cell differentiation, we used adenoviral vectors to selectively activate or inactivate these pathways. We found that the selective activation of Erk pathways suppressed Schwann cell differentiation, whereas that of PI3K pathways promoted it. Furthermore, lithium chloride, a modulator of glycogen synthase kinase-3beta (GSK-3beta) promoted Schwann cell differentiation, suggesting the involvement of GSK-3beta as a downstream molecule of PI3K-Akt pathways. Selective activation of PI3K pathways in Schwann cells by gene transfer also demonstrated increased myelination in in vitro Schwann cell-DRG neuron cocultures and in vivo allogenic nerve graft experiments. We conclude that signals mediated by PI3K-Akt are crucial for initiation of myelination and that the effects of growth factors are primarily dependent on the balance between Erk and PI3K-Akt activation. Our results also propose the possibility of augmenting Schwann cell functions by modulating intracellular signals in light of future cell therapies.

Animals↗

Postoperative expansion of intramedullary high-intensity areas on T2-weighted magnetic resonance imaging after cervical laminoplasty.

STUDY DESIGN: A cohort study. OBJECTIVE: To determine the frequency of swelling of the spinal cord with an intramedullary lesion occurring after laminoplasty for nontraumatic cervical myelopathy and the possible mechanism of postoperative motor paresis of the upper extremity. SUMMARY OF BACKGROUND DATA: Postoperative enlargement of the spinal cord with an intramedullary lesion after decompression surgery for cervical stenotic myelopathy has been reported. But the frequency of the incidence remains unknown. Postoperative motor paresis occurring mainly in the C5 and C6 segments is known but various theories on its etiology exist, including the root involvement hypothesis and the spinal cord impairment hypothesis. Thus, the etiology is controversial. METHODS: One hundred fourteen patients with cervical stenotic myelopathy were included in this study. All of them underwent preoperative magnetic resonance imaging and postoperative magnetic resonance imaging 3 weeks after surgery. We watched for the occurrence of postoperative neurologic deterioration including paralysis of the upper extremities. We also observed the presence or absence of postoperative abnormal expansion of T2 high-signal intensity areas on magnetic resonance imaging in the spinal cord. RESULTS: Seven patients (6.1%) showed postoperative abnormal expansion of the T2 high-signal intensity area; 3 of the 7 were asymptomatic. A total of 9 patients (7.9%) experienced unilateral upper motor paresis after surgery. In 4 of the 9 cases, paresis of the unilateral deltoid, biceps and brachialis muscles (proximal paresis) occurred between 4 and 6 days after surgery. None of the 4 showed postoperative abnormal expansion of the T2 high-signal intensity area. In 3 other of the 9 patients, distal paresis occurred just after surgical intervention. Two of the 3 showed postoperative abnormal expansion of the T2 high-signal intensity area and 1 showed slight expansion of the area. In the other 2 cases, diffuse paresis occurred, and their postoperative magnetic resonance imaging showed abnormal expansion of the T2 high-signal intensity area. CONCLUSIONS: Spinal cord enlargement with abnormal expansion of the T2 high-signal intensity area, although not common, is an unpreventable complication after laminoplasty. This was strongly related with distal and diffuse type of postoperative paresis of the upper extremity without deterioration of lower motor function, but was little associated with a proximal type of paresis, so-called C5 and C6 palsies.

Aged↗

SRC-1 is necessary for skeletal responses to sex hormones in both males and females.

UNLABELLED: We created SRC-1(-/-) mice by mating floxed SRC-1 mice with CMV-Cre transgenic mice. The SRC-1(-/-) mice showed high turnover osteopenia under physiological conditions and hardly responded to osteoanabolic actions of exogenous androgen and estrogen in males and females, respectively, after gonadectomies, indicating that SRC-1 is essential for the maintenance of bone mass by sex hormones. INTRODUCTION: Steroid receptor coactivator-1 (SRC-1) is the first identified coactivator of nuclear receptors. This study investigated the role of SRC-1 in skeletal tissues of males and females using the deficient (SRC-1(-/-)) mice. MATERIALS AND METHODS: SRC-1(-/-) mice were generated by mating our original floxed SRC-1 mice with CMV-Cre transgenic mice. Bone metabolism between 24-week-old SRC-1(-/-) and wildtype (WT) littermates under physiological conditions was compared in males and females by radiological, histological, and biochemical analyses. Difference of skeletal responses to steroid hormones was examined by gonadectomies and exogenous administration experiments with the hormones. Statistical analysis was performed by ANOVA determined by posthoc testing using Bonferroni's method. RESULTS AND CONCLUSIONS: Although SRC-1(-/-) mice showed no abnormality in growth or major organs, both males and females showed osteopenia with high bone turnover in the trabecular bones, but not in the cortical bones, compared with WT littermates. Their serum levels of sex hormones were upregulated, suggesting a compensatory reaction for the insensitivity to these hormones. Gonadectomies caused decreases in BMDs of SRC-1(-/-) and WT mice to the same levels; however, replacement with 5 alpha-dihydrotestosterone and 17 beta-estradiol in males and females, respectively, failed to restore the bone loss in SRC-1(-/-), whereas the WT bone volume was increased to the sham-operated levels. In contrast, bone loss by administered prednisolone was similarly seen in SRC-1(-/-) and WT mice. We conclude that SRC-1 is essential for the maintenance of bone mass by sex hormones, but not for the catabolic action of glucocorticoid, under both physiological and pathological conditions.

Animals↗

Osteoclast differentiation by RANKL requires NF-kappaB-mediated downregulation of cyclin-dependent kinase 6 (Cdk6).

UNLABELLED: This study investigated the involvement of cell cycle factors in RANKL-induced osteoclast differentiation. Among the G1 cell cycle factors, Cdk6 was found to be a key molecule in determining the differentiation rate of osteoclasts as a downstream effector of the NF-kappaB signaling. INTRODUCTION: A temporal arrest in the G1 phase of the cell cycle is a prerequisite for cell differentiation, making it possible that cell cycle factors regulate not only the proliferation but also the differentiation of cells. This study investigated cell cycle factors that critically influence differentiation of the murine monocytic RAW264.7 cells to osteoclasts induced by RANKL. MATERIALS AND METHODS: Growth-arrested RAW cells were stimulated with serum in the presence or absence of soluble RANKL (100 ng/ml). Expressions of the G1 cell cycle factors cyclin D1, D2, D3, E, cyclin-dependent kinase (Cdk) 2, 4, 6, and Cdk inhibitors (p18 and p27) were determined by Western blot analysis. Involvement of NF-kappaB and c-jun N-terminal kinase (JNK) pathways was examined by overexpressing dominant negative mutants of the IkappaB kinase 2 (IKK(DN)) gene and mitogen-activated protein kinase kinase 7 (MKK7(DN)) gene, respectively, using the adenovirus vectors. To determine the direct effect of Cdk6 on osteoclast differentiation, stable clones of RAW cells transfected with Cdk6 cDNA were established. Osteoclast differentiation was determined by TRACP staining, and cell cycle regulation was determined by BrdU uptake and flow cytometric analysis. RESULTS AND CONCLUSION: Among the cell cycle factors examined, the Cdk6 level was downregulated by RANKL synchronously with the appearance of multinucleated osteoclasts. Inhibition of the NF-kappaB pathway by IKK(DN) overexpression, but not that of the JNK pathway by MKK7(DN) overexpression, caused the decreases in both Cdk6 downregulation and osteoclastogenesis by RANKL. RAW cells overexpressing Cdk6 resist RANKL-induced osteoclastogenesis; however, cell cycle regulation was not affected by the levels of Cdk6 overexpression, suggesting that the inhibitory effect of Cdk6 on osteoclast differentiation was not exerted through cell cycle regulation. These results indicate that Cdk6 is a critical regulator of RANKL-induced osteoclast differentiation and that its NF-kappaB-mediated downregulation is essential for efficient osteoclast differentiation.

Animals↗

Measurement of occipitocervical angle.

STUDY DESIGN: This study compared the reliability of 3 techniques used to measure alignment between the occiput and cervical spine. OBJECTIVES: Intraobserver and interobserver intraclass correlation coefficient were computed to determine the most reliable method to measure occipitocervical angle. SUMMARY OF BACKGROUND DATA: No studies have been performed comparing occipitocervical angle measurement techniques. METHODS: The angles between the inferior endplate of second cervical vertebrae and the occiput line using the Chamberlain line, McRae line, and McGregor line were measured from lateral cervical radiographs of 30 healthy volunteers. Five spine surgeons made measurements. RESULTS: Mean intraobserver variances of the angles using Chamberlain line, McRae line, and McGregor line were 2.0 degrees (ranging from 0 degrees-15 degrees), 4.7 degrees (from 0 degrees-28 degrees), and 1.5 degrees (from 0 degrees-9 degrees), respectively; intraobserver intraclass correlation coefficients of the angles were 0.956, 0.835, and 0.975. Mean interobserver variances of the angles using Chamberlain line, McRae line, and McGregor line were 2.3 degrees (from 0.4 degrees-6.4 degrees), 5.0 degrees (from 1.8 degrees-11.9 degrees), and 1.4 degrees (from 0 degrees-4.5 degrees), respectively; interobserver intraclass correlation coefficients were 0.939, 0.802, and 0.972. The highest reliability indexes were obtained for McGregor line. CONCLUSIONS: The McGregor line is the most reproducible and reliable method for measurement of the occipitocervical angle.

Anthropometry↗

Simple curettage without bone grafting for enchondromas of the foot.

BACKGROUND: Simple curettage without bone grafting for enchondromas of the hand and its good clinical results have been reported. Yet, there have been no reports regarding simple curettage without bone grafting for enchondromas of the foot. The purpose of this study is to elucidate the clinical results of this method for enchondromas of the foot. METHODS: We studied eight patients (ten bones) with enchondromas of the foot treated with simple curettage without bone grafting. After making an oval or round fenestration, the enchondroma was curetted. The cortical window of the fenestration was excised in five bones, whereas it was replaced at the fenestration site in the other five bones. RESULTS: The affected toe was immobilized with a tape in two patients. All patients began to walk on the day of surgery or the next day without crutches. Sclerotic changes on the plain radiographs were seen 6.4 weeks (range: 4-10 weeks) postoperatively. The patients returned to their normal daily activity including occupation and sport in 8.6 weeks (range: 0-12 weeks) postoperatively. The radiographic appearance was almost normalized in 8.4 months on average (range: 3-14 months). Function was classified as excellent in all bones according to a modified Tordai classification. CONCLUSION: We conclude that simple curettage without bone grafting can be one of the standard surgical treatments for enchondromas of the foot.

Adult↗

Impact of degenerative spinal diseases on bone mineral density of the lumbar spine in elderly women.

Degenerative diseases of lumbar spine commonly noted in elderly people may affect their lumbar spine bone mineral density (BMD). The aim of this study is to determine whether the degree of degenerative spinal diseases is correlated with lumbar spine and femoral neck BMD. This study included 630 women age 60 years or over (mean age 73.3 +/- 6.9 years) visiting the Osteoporosis Outpatient Clinic at the Tokyo Metropolitan Geriatric Medical Center. Subjects underwent anteroposterior and lateral X-rays of the lumbar spine. The score of degenerative spinal diseases for each subject was calculated according to the scores for the Kellgren-Lawrence method, osteophyte formation, bone sclerosis, disk space narrowing, and spondylolisthesis involving L1-L2 through L4-L5 interspaces. Moreover, the number of vertebral fractures at L2 through L4 was recorded. The BMD of the second to fourth lumbar spine from anteroposterior projections and femoral neck were measured using an Expert-5000 (GE Lunar, Madison, WI USA). Most subjects had degenerative diseases of the lumbar spine. Scores for the Kellgren-Lawrence method, osteophyte formation, bone sclerosis, disk space narrowing, and spondylolisthesis were positively correlated with lumbar spine BMD, while they were not correlated with femoral neck BMD. Multiple regression analysis indicated that the scores for osteophyte formation, bone sclerosis, and disk space narrowing were independently correlated with lumbar spine BMD. Thus, in this study, the scores for degenerative spinal diseases were correlated with lumbar spine BMD, while they were not correlated with femoral neck BMD. This discrepancy indicates that degenerative spinal diseases are associated with increased lumbar spine BMD measurements. Femoral neck BMD therefore may be more appropriate than lumbar spine BMD in evaluating osteoporosis in elderly women.

Aged↗

Effects of antithrombin III on spinal cord-evoked potentials and functional recovery after spinal cord injury in rats.

STUDY DESIGN: From the view of motor function, spinal cord-evoked potentials, and histology, we evaluated the effects of antithrombin III on a spinal cord injury resulting in incomplete paraplegia. OBJECTIVES: To investigate the effect of antithrombin III on the recovery process after acute incomplete rat spinal cord injury. SUMMARY OF BACKGROUND DATA: Antithrombin III is used for treating disseminated intravascular coagulation by its anticoagulant effect and is also reported to reduce organ damage by the release of prostaglandin I2 from endothelial cells, induced by antithrombin III. Therefore, antithrombin III has potential as a therapeutic agent for spinal cord damage. METHODS: The spinal cord injury was induced by placing a 25 g weight on the dorsal surface of the spinal cord at the 10th thoracic spine level for 20 minutes. Antithrombin III (250 U/kg) was administered intravenously 5 minutes before the compression, whereas 2 mL of physiologic saline solution was administered to the control group. We recorded the spinal cord-evoked potentials at the T13 level after stimulation of the brain and C7 level. For 12 weeks after the injury, we observed the recovery course of waveform and motor function. The recovery of motor function was evaluated by using inclined table and modified Tarlov scores. We also examined the histology of the compressed site in the spinal cord. RESULTS: There were statistically significant differences in the motor recovery process between the two groups. Evoked potentials of the antithrombin III group recovered earlier than those of the control group. Histologically, hemorrhage and tissue defects in the spinal cord were less in the antithrombin III group. CONCLUSION: Because antithrombin III facilitated the recovery of behavior and evoked potentials, these findings suggest that antithrombin III may have a positive effect on the recovery of incomplete spinal cord injury.

Animals↗

Impairment of bone healing by insulin receptor substrate-1 deficiency.

Insulin receptor substrate-1 (IRS-1) is an essential molecule for intracellular signaling of insulin-like growth factor (IGF)-I and insulin, both of which are potent anabolic regulators of bone and cartilage metabolism. To investigate the role of IRS-1 in bone regeneration, fracture was introduced in the tibia, and its healing was compared between wild-type (WT) mice and mice lacking the IRS-1 gene (IRS-1(-/-) mice). Among 15 IRS-1(-/-) mice, 12 remained in a non-union state even at 10 weeks after the operation, whereas all 15 WT mice showed a rigid bone union at 3 weeks. This impairment was because of the suppression of callus formation with a decrease in chondrocyte proliferation and increases in hypertrophic differentiation and apoptosis. Reintroduction of IRS-1 to the IRS-1(-/-) fractured site using an adenovirus vector significantly restored the callus formation. In the culture of chondrocytes isolated from the mouse growth plate, IRS-1(-/-) chondrocytes showed less mitogenic ability and Akt phosphorylation than WT chondrocytes. An Akt inhibitor decreased the IGF-I-stimulated DNA synthesis of chondrocytes more potently in the WT culture than in the IRS-1(-/-) culture. We therefore conclude that IRS-1 deficiency impairs bone healing at least partly by inhibiting chondrocyte proliferation through the phosphatidylinositol 3-kinase/Akt pathway, and we propose that IRS-1 can be a target molecule for bone regenerative medicine.

Adenoviridae↗