Biomedical subjects

Yuji Kasukawa

Publications and source records attributed to Yuji Kasukawa.

17 recordsLinked to original sources

PubMed2006

Whole genome microarray analysis of growth hormone-induced gene expression in bone: T-box3, a novel transcription factor, regulates osteoblast proliferation.

Growth hormone (GH) is important in the development and maintenance of bone; however, the IGF-dependent and -independent molecular pathways involved remain to be established. We used microarray analysis to evaluate GH signaling pathways in 4-wk-old GH-deficient mice following a single injection of GH (4 mg/kg body wt) or PBS (n = 6/group) at 6 or 24 h after treatment. Six thousand one hundred sixty genes were differentially expressed at P </= 0.05, and 17% of these genes were identified at both time points. Several of the genes differentially expressed were expressed sequence tags, and the remaining genes fell into 49 Gene Ontology categories. For subsequent studies, we focused on T-box (Tbx)3, a novel transcription factor, which increased more than twofold at both time points. Real-time RT-PCR analysis determined that pretreatment with IGF-binding protein-4 did not block GH-induced Tbx3 expression in vitro. Pretreatment with TNF-alpha blocked GH-induced Tbx3 expression. Tbx3 expression increased during osteoblast differentiation and following BMP-7 and Wnt3a treatment (P </= 0.05). Blocking Tbx3 expression by small interfering RNA decreased cell number and [(3)H]Thymidine incorporation (P < 0.01). In conclusion, 1) GH caused acute changes in several novel genes, suggesting that many GH-induced signaling pathways and target genes remain to be discovered; 2) because Tbx3 expression is regulated in osteoblasts and blockage of Tbx3 expression decreased cell number and DNA synthesis, we propose that Tbx3 is an important determinant of osteoblast cell number.

Animals↗

PubMed2006

Dural substitute with polyglycolic acid mesh and fibrin glue for dural repair: technical note and preliminary results.

BACKGROUND: An ideal dural substitute that enables watertight closure, has sufficient strength, and can be absorbed without remnant materials that induce inflammation, adhesion, and infection is not available. The purpose of this study was to evaluate the efficacy of a bioabsorbable polyglycolic acid (PGA) mesh and fibrin glue as a substitute for dural repair. METHODS: Altogether, 10 patients with noted dural tears during extradural spinal surgery and 20 patients who underwent durotomy for intradural spinal surgery were included in this study. In a series of 20 consecutive cases, dural closure was performed by suture and fibrin glue. In the subsequent 10 consecutive patients, dural closure was performed by suture and fibrin glue with the use of absorbable PGA mesh. The medical records and magnetic resonance imaging (MRI) of the surgical site were retrospectively reviewed to evaluate the presence of a cerebrospinal fluid (CSF) fistula or leakage after the surgery. RESULTS: A CSF fistula occurred in five patients who underwent dural repair with fibrin glue alone, and postoperative MRI showed CSF leakage in two patients with incidental dural tears after laminectomy for ossification of ligamentum flavum. No CSF fistula was present in patients who underwent dural repair using PGA mesh and fibrin glue, and no adverse effects or complications were encountered postoperatively. Follow-up MRI revealed no evidence of CSF leakage around the reconstructed dura mater. CONCLUSIONS: The use of PGA mesh and fibrin glue for the repair of dura mater is a useful method of preventing CSF leakage in spinal surgery.

Adolescent↗

PubMed2006

Clinical features of cauda equina tumors requiring surgical treatment.

In this study, we evaluated the clinical features of cauda equina tumors requiring surgical treatment. Medical records of 28 patients with cauda equina tumors (13 men and 15 women) undergoing surgical treatment were retrospectively reviewed. The majority of histological diagnoses indicated schwannoma (23 cases, 82%), and the remaining 5 indicated ependymoma, neurofibroma, meningioma, and ganglioneuroblastoma. In 86% of the cases, the initial symptom was pain in the lower back and/or lower extremities. Preoperatively, half of the patients had symmetrical pain in the lower back or lower extremities, severe pain in the supine position, or pain that was increased by coughing. One third of the patients needed morphine to control nocturnal pain. Tumor size, as determined by magnetic resonance imaging (MRI), correlated with preoperative symptom duration (r = 0.66, p < 0.001). These findings indicate that symmetrical lower back pain and/or pain that radiates to both lower extremities and increases in the supine position are characteristic of cauda equina tumors. The correlation between symptom duration and tumor size indicates that earlier diagnosis of this tumor is necessary. Earlier diagnosis based on these characteristic symptoms should make use of further examinations such as MRI.

Adolescent↗

PubMed2006

Chronic subdural hematoma coexisting with ligamentum flavum hematoma in the lumbar spine: a case report.

We present a case of a chronic spinal subdural hematoma combined with a ligamentum flavum hematoma in the lumbar spine treated surgically. An 83-year-old woman receiving antiplatelet medicine due to an angina suffered from pain in her lower extremity and gait disturbance after a backward fall. Radiological findings including magnetic resonance imaging (MRI) revealed hematoma in the ligamentum flavum at the level of L2 - L3 and a chronic subdural hematoma at the level from L3 to L5. Laminectomy through L2 to L5 was performed and a hematoma existing in the ligamentum flavum and cystic mass was removed. A chronic subdural hematoma was spontaneously evacuated after splitting of the dura mater and an intact arachnoid membrane was observed with no leakage of cerebrospinal fluid. Her clinical symptoms completely disappeared after surgery. To the best of our knowledge, this is the first case of combination of chronic subdural hematoma and ligamentum flavum hematoma in the lumbar spine treated by surgery. Chronic spinal subdural hematoma and hematoma in the ligamentum flavum should be considered as a cause of progressive nerve root compression in patients with anticoagulant therapy, and an appropriate pre-operative diagnosis would be needed to achieve complete decompression of subdural and epidural hematoma.

Aged, 80 and over↗

PubMed2006

Ligamentum flavum hematoma in the cervical spine - case report.

A 67-year-old man presented with a rare case of ligamentum flavum hematoma manifesting as progressive tetraplegia following cervical traction therapy. Magnetic resonance imaging of the cervical spine showed a posterior mass that was continuous with the ligamentum flavum at the C3-4 levels. Complete resection of the mass that contained brownish hemorrhage was performed, resulting in excellent symptom relief. We speculate that repeated trivial trauma to the degenerative ligamentum flavum was the main predisposing factor in the present case. Ligamentum flavum hematoma is a rare cause of spinal root or cord compression which typically occurs in the lower thoracic or lumbar spine, but may also appear in the cervical spine.

Aged↗

PubMed2006

Decompression of idiopathic lumbar epidural lipomatosis: diagnostic magnetic resonance imaging evaluation and review of the literature.

OBJECT: Idiopathic symptomatic spinal epidural lipomatosis (SEL) is a rare condition, and few reports have discussed diagnostic imaging criteria. To evaluate factors relating to its clinical symptoms, correlations between clinical features and the presence of spinal epidural fat were investigated, and the literature concerning idiopathic SEL was reviewed. METHODS: Morphological gradings of epidural fat were evaluated in seven patients with idiopathic SEL by using magnetic resonance (MR) imaging. In addition, body mass index (BMI), the number of involved vertebral levels, grade, and preoperative Japanese Orthopaedic Association (JOA) score were analyzed. Surgery resulted in symptomatic relief, with a mean JOA score recovery rate of 67.4%. Grading of epidural fat tended to display a slight negative correlation with preoperative JOA score, whereas a strong significant positive correlation was found between the number of involved vertebral levels and BMI. CONCLUSIONS: The number of involved vertebral levels and obesity are strongly correlated, whereas severity of dural compression is not always significantly associated with neurological complications. These results indicate that epidural fat of the lumbar spine contributes to neurological deficits. In addition, weight-reduction therapy appears to decrease the number of vertebral levels involved. Magnetic resonance imaging-based grading is helpful for the diagnosis and evaluation of idiopathic lumbar SEL. Moreover, symptoms and neurological findings are important for determining the surgical approach.

Adipose Tissue↗

PubMed2006

Spondylolisthesis of the thoracic spine. Case report.

The thoracic spine is stabilized in the anteroposterior direction by the rib cage and the facet joints. Spondylolisthesis of the thoracic spine is less common than that of the lumbar spine. The authors describe a rare case of thoracic spondylolisthesis in which the patient suffered back pain and myelopathy. The patient was a 44-year-old woman. Plain radiography revealed Grade I T11-12 spondylolisthesis. The pedicle-facet joint angle at T-11 was 118 degrees, greater than that of T-10 or T-12. Postmyelography computerized tomography scanning revealed posterior compression of the dural sac as well as enlargement of and degenerative changes in the facet joint at T-11. Magnetic resonance imaging showed anterior and posterior compression of the spinal cord at the level of the spondylolisthesis. To achieve posterior T10-12 decompression, the surgeons performed a laminectomy and posterolateral fusion in which a pedicle screw fixation system was placed. The patient's back pain disappeared immediately after the operation. The authors conclude that the enlargement of the pedicle-facet joint angle and the degenerative changes of the facet joint caused the thoracolumbar spondylolisthesis.

Adult↗

PubMed2005

Ligamentum flavum hematoma in the rigid thoracic spinal segments: case report.

Ligamentum flavum hematoma, a rare cause of spinal nerve root and canal compression, typically occurs in the mobile lumbar spine segments. A thoracic ligamentum flavum hematoma is extremely rare--only one such case of a thoracolumbar (T11-12) lesion has been reported. The thoracolumbar region with its floating ribs, however, is structurally and biomechanically similar to the lumbar spine and its mobility is greater than the higher thoracic levels. To the best of their knowledge, the authors report the first case of a ligamentum flavum hematoma in the region of the rigid thoracic spinal segments with the contiguous rib cage. A symptomatic T9-10 ligamentum flavum hematoma is described in the case of a 66-year-old woman with compensatory thoracic lordosis secondary to the lumbar degenerative kyphosis. The hematoma was removed and the diagnosis was histologically confirmed. The authors speculate that thoracic lordosis might have contributed to the development of the hematoma because the ligamentum flavum and the facet joint were subjected to greater axial stress than in individuals with normal spinal alignment.

Aged↗

PubMed2004

Insulin-like growth factor-binding protein-5 induces a gender-related decrease in bone mineral density in transgenic mice.

IGF-binding protein-5 (IGFBP-5) is abundant in serum and bone during normal skeletal development, but levels decrease in osteoporosis. Studies have shown that IGFBP-5 stimulates markers of bone formation by potentiating IGF actions and by IGF-independent actions. To test the hypothesis that IGFBP-5 promotes the acquisition of bone mineral density (BMD), we generated transgenic (Tg) mice overexpressing Igfbp5 using a cytomegalovirus enhancer and beta-actin promoter (CMV/betaA). Tg animals showed an increase in serum IGFBP-5 concentrations by 7.7- to 3.5-fold at 3-8 wk of age, respectively. Concentrations were 6-49% higher for males compared with females in both wild-type and Tg mice. Surprisingly, BMD decreased in a gender-dependent manner, with Tg male adults affected more severely than Tg females (31.3% vs. 19.2% reduction, respectively, compared with wild-type mice, assessed by dual energy x-ray absorptiometry). Significant gender differences in BMD were confirmed by peripheral quantitative computed tomography. Histomorphometry revealed that although the bone formation rate and mineralizing surface at the periosteum decreased in Tg mice, they increased at the endosteum, suggesting opposing effects of IGFBP-5 on periosteal and endosteal osteoblasts (by altering proliferation or survival). These findings differ from previous observations in Igf1- and Igf2-null animals. In conclusion, IGFBP-5 has a significant influence on BMD acquisition and maintenance that is dependent on gender and age. The phenotype of Igfbp5 mice cannot be explained solely by IGF inhibition; thus, this study provides the first in vivo evidence, by genetic manipulation, for IGF-independent actions of IGFBP-5 in bone function. These findings have implications for the gender-biased progression of osteoporosis.

Absorptiometry, Photon↗

PubMed2004

Effects of secreted frizzled-related protein 3 on osteoblasts in vitro.

UNLABELLED: To examine if sFRP3s act as decoy receptors for Wnt, we examined the effects of recombinant sFRP3 on mouse osteoblast proliferation and differentiation. We found that sFRP3 unexpectedly increased osteoblast differentiation, suggesting it may act through other mechanisms besides acting as a decoy receptor for Wnt's. INTRODUCTION: Secreted frizzled-related proteins (sFRPs) are a truncated form of frizzled receptor, missing both the transmembrane and cytosolic domains. Because previous studies have shown that sFRPs bind and act as decoy receptors for Wnt proteins that promote osteoblast differentiation, we postulated that sFRP3 acts as an inhibitor of osteoblast differentiation. MATERIALS AND METHODS: We examined the effects of mouse recombinant sFRP3 and/or Wnt-3A on cell proliferation and differentiation using MC3T3-E1 mouse osteoblasts and primary cultures of mouse bone marrow stromal cells. We evaluated the effects of sFRP3 on beta-catenin levels using Western immunoblot analyses. RESULTS: We found that sFRP3 suppressed osteoblast cell number in a dose-dependent manner that was the result of a decrease in proliferation and not because of an increase in apoptosis. Surprisingly, sFRP3 increased osteoblast differentiation, which could not be explained based on sFRP3 acting as a decoy receptor for stimulatory Wnt's. Furthermore, sFRP3 did not inhibit Wnt3A-induced increase in alkaline phosphatase (ALP) activity. Wnt3A, but not sFRP3 treatment, increased cellular beta-catenin levels, and sFRP3 failed to block Wnt3A-induced increase in cellular beta-catenin levels. Treatment with endostatin, an agent known to degrade beta-catenin, did not inhibit sFRP3-induced increase in ALP activity. sFRP1, like sFRP3, inhibited proliferation and stimulated ALP activity in MC3T3-E1 mouse osteoblasts. CONCLUSIONS: Based on our findings, we conclude that sFRP3 decreased osteoblast proliferation and unexpectedly increased parameters of osteoblast differentiation. Based on our findings, we propose that sFRP3 may stimulate differentiation through a beta-catenin-independent pathway in addition to its previously known function as a decoy receptor for Wnt's.

Animals↗

PubMed2004

The anabolic effects of GH/IGF system on bone.

Osteoporosis is the result of imbalance in bone remodeling caused by increased bone resorption and decreased bone formation. In terms of the mechanisms for the age-related impairment in bone formation, a deficiency in growth hormone (GH)/insulin-like growth factor (IGF) system that occurs with age has been proposed to play a major role. The potential causes for age-related decline in GH secretion are under active investigation and may involve multiple mechanisms including GH secretagogues, sex hormones, nutritional status and physical activity. Although a number of animal and clinical studies have provided experimental evidence for potential use of GH/IGF system components to increase bone mass, the clinical utility of GH/IGF system components for treatment of osteoporosis has not come to fruition because of our incomplete understanding of the regulation of production and actions of GH/IGF system components. Regarding the actions of GH in target tissues, there is evidence that IGF system plays a major role in mediating the GH effects. In addition, GH may also exert effects on certain target tissues independent of IGFs. It is also known that GH effects on target tissue involve multiple components of the IGF system including the ligands, receptors, IGF binding proteins (IGFBP), IGFBP proteases and activators and inhibitors of IGFBP proteases. Future studies on the mechanisms that contribute to age-related impairment in GH/IGF axis and the molecular pathways that contribute to the bone forming effects of GH/IGF axis may provide a foundation for the development of safe and effective therapies involving one or more IGF system components to correct bone formation deficit in the elderly subjects.

Animals↗

PubMed2003

Lack of insulin-like growth factor I exaggerates the effect of calcium deficiency on bone accretion in mice.

Recent studies provide evidence that the GH/IGF-I axis plays a critical role in the regulation of bone accretion that occurs during puberty and that the peak bone mineral density (BMD) is dependent on the amount of dietary calcium intake during the active growth phases. To evaluate whether IGF-I deficiency exaggerates the effect of calcium deficiency on bone accretion during active growth phases, IGF-I knockout (KO) and wild-type (WT) mice were fed with low calcium (0.01%) or normal calcium (0.6%) for 2 wk during the pubertal growth phase and were labeled with tetracycline. The low calcium diet caused significant decreases in endosteal bone formation parameters and a much greater increase in the resorbing surface of both the endosteum and periosteum of the tibia of IGF-I KO mice compared with WT mice. Accordingly, femur BMD measured by dual energy x-ray absorptiometry or peripheral quantitative computed tomography increased significantly in IGF-I WT mice fed the low calcium diet, but not in IGF-I KO mice. IGF-I-deficient mice fed the normal calcium diet showed elevated PTH levels, decreased serum 1,25-dihydroxyvitamin D and serum calcium levels at baseline. Serum calcium changes due to calcium deficiency were greater in IGF-I KO mice compared with WT mice. PTH levels were 7-fold higher in IGF-I KO mice fed normal calcium compared with WT mice, which was further elevated in mice fed the low calcium diet. Treatment of IGF-I-deficient lit/lit mice with GH decreased the serum PTH level by 70% (P < 0.01). Based on these and past findings, we conclude that: 1) IGF-I deficiency exaggerates the negative effects of calcium deficiency on bone accretion; and 2) IGF-I deficiency may lead to 1,25-dihydroxyvitamin D deficiency and elevated PTH levels even under normal calcium diet.

Absorptiometry, Photon↗

PubMed2003

Osteoporotic vertebral fracture adjacent to a nonsegmented hemivertebra.

A combination of osteoporotic vertebral fractures and congenital spinal deformity is theoretically possible, but there have been no reports on this combination in the literature. We describe a rare case of an osteoporotic vertebral fracture adjacent to the nonsegmented hemivertebra. A 60-year-old postmenopausal woman who did not recall any specific trauma presented with severe back pain. She had markedly decreased bone mineral density and significant lumbar kyphoscoliosis with a nonsegmented hemivertebra between L1 and L2 on radiographs of the lumbar spine. Magnetic resonance imaging (MRI) revealed a vertebral fracture adjacent to the nonsegmented hemivertebra. Laboratory studies showed increased serum bone-specific alkaline phosphatase (BAP) and urinary type I collagen crosslinked N-telopeptide (NTx). A thoracolumbar brace was applied for 3 months. Daily administration of alendronate normalized her serum BAP and urinary NTx levels. MRI scans of the lumbar spine after 6 months also confirmed normalized signal intensities of the fractured vertebra adjacent to the nonsegmented hemivertebra. The vertebral fracture seemed to be induced by spinal malalignment, increased stress on the adjacent level of the fused segment, and its fragility due to osteoporosis.

Bone Malalignment↗

PubMed2003

In vivo bone formation in fracture repair induced by direct retroviral-based gene therapy with bone morphogenetic protein-4.

This study sought to develop an in vivo gene therapy to accelerate the repair of bone fractures. In vivo administration of an engineered viral vector to promote fracture healing represents a potential high-efficacy, low-risk procedure. We selected a murine leukemia virus (MLV)-based retroviral vector, because this vector would be expected to target transgene expression to the proliferating periosteal cells arising shortly after bone fracture. This vector transduced a hybrid gene that consisted of a bone morphogenetic protein (BMP)-4 transgene with the BMP-2 secretory signal to enhance the secretion of mature BMP-4. The MLV vector expressing this BMP-2/4 hybrid gene or beta-galactosidase control gene was administered at the lateral side of the fracture periosteum at 1 day after fracture in the rat femoral fracture model. X-ray examination by radiograph and peripheral quantitative computed tomography at 7, 14, and 28 days after fracture revealed a highly significant enhancement of fracture tissue size in the MLV-BMP-2/4-treated fractures compared to the control fractures. The tissue was extensively ossified at 14 and 28 days, and the newly formed bone exhibited normal bone histology. This tissue also exhibited strong immunohistochemical staining of BMP-4. Additional control and MLV-BMP-2/4-treated animals each were monitored for 70 days to determine the fate of the markedly enhanced fracture callus. Radiographs showed that the hard callus had been remodeled and substantial healing at the fracture site had occurred, suggesting that the union of the bone at the fracture site was at least as high in the BMP-4-treated bone as in the control bone. There was no evidence of viral vector infection of extraskeletal tissues, suggesting that this in vivo gene therapy for fracture repair is safe. In summary, we have demonstrated for the first time that a MLV-based retroviral vector is a safe and effective means of introducing a transgene to a fracture site and that this procedure caused an enormous augmentation of fracture bone formation.

Animals↗

PubMed2003

Evidence that sensitivity to growth hormone (GH) is growth period and tissue type dependent: studies in GH-deficient lit/lit mice.

We previously found that the magnitude of skeletal deficits caused by GH deficiency varied during different growth periods. To test the hypothesis that the sensitivity to GH is growth period dependent, we treated GH-deficient lit/lit mice with GH (4 mg/kg body weight.d) or vehicle during the prepubertal and pubertal (d 7-34), pubertal (d 23-34), postpubertal (d 42-55), and adult (d 204-217) periods and evaluated GH effects on the musculoskeletal system by dual energy x-ray absorptiometry (DEXA) and peripheral quantitative computed tomography. GH treatment during different periods significantly increased total body bone mineral content, bone mineral density (BMD), bone area, and lean body mass and decreased percentage of fat compared with vehicle; however, the magnitude of change varied markedly depending on the treatment period. For example, the increase in total body BMD was significantly (P < 0.01) greater when GH was administered between d 42-55 (15%) compared with pubertal (8%) or adult (7.7%) periods, whereas the net loss in percentage of body fat was greatest (-56%) when GH was administered between d 204 and 216 and least (-27%) when GH was administered between d 7 and 35. To determine whether GH-induced anabolic effects on the musculoskeletal system are maintained after GH withdrawal, we performed DEXA measurements 3-7 wk after stopping GH treatment. The increases in total body bone mineral content, BMD, and lean body mass, but not the decrease in body fat, were sustained after GH withdrawal. Our findings demonstrate that the sensitivity to GH in target tissues is growth period and tissue type dependent and that continuous GH treatment is necessary to maintain body fat loss but not BMD gain during a 3-7 wk follow-up.

Absorptiometry, Photon↗

PubMed2003

Factors related to long-term outcome after decompressive surgery for ossification of the ligamentum flavum of the thoracic spine.

OBJECT: Factors related to long-term surgical outcome of thoracic myelopathy caused by ossification of the ligamentum flavum (OLF) have not been fully investigated. To evaluate these factors, the authors reviewed medical records obtained in patients who had undergone decompressive surgery for thoracic OLF. METHODS: Thirty-four patients in whom decompressive surgery was performed for thoracic OLF (mean follow-up period 8 years) were recruited. Fourteen patients underwent simultaneous decompressive surgery for cervical or lumbar lesions. Patient age, duration of symptoms, OLF type, dural adhesion, neurological status classified by the Japanese Orthopaedic Association (JOA) scale before and after surgery (1 month postoperatively and at final follow up), and recovery rate were reviewed. The ossified ligamentum flavum was classified into five types according to Sato's classification by assessing preoperative computerized tomography scans. The mean preoperative JOA score (5) was significantly improved at 1 month after surgery (7.1) and at final follow up (7.9) (p < 0.05). Recovery rates at 1 month and at final follow up were 34.6 and 44.2%, respectively. No significant correlations were found between age, OLF type, and neurological status before and after surgery. In patients with dural adhesion, which was observed in cases of larger-type OLF (p < 0.02), lower JOA scores were observed compared with those in patients without dural adhesion both preoperatively and at 1 month after surgery (p < 0.05) but not at the final follow-up examination. Higher JOA scores and recovery rates were demonstrated in patients who had undergone simultaneous surgery than in those who had not undergone simultaneous surgery at 1 month (p < 0.05) but not at the final follow up. Using multiple regression analysis, the authors identified the duration of preoperative symptoms as the most important predictor of a high JOA score and recovery rate at the final follow up. CONCLUSIONS: Duration of preoperative symptoms represents the most important predictor of long-term surgery-related outcome in patients treated for thoracic OLF. The type of ossified ligamentum flavum, dural adhesion, and simultaneous surgery for coexistent cervical or lumbar lesions do not appear to influence the long-term postoperative prognosis.

Adult↗

PubMed2002

Insulin-like growth factor I effect on the number of osteoblast progenitors is impaired in ovariectomized mice.

Because insulin-like growth factor (IGF) I is an important regulator of bone formation, we proposed the hypothesis that IGF-I could contribute in regulating the number of osteoblast progenitors (colony-forming unit fibroblast with ALP activity [CFU-F/ALP+]). To test ex vivo and in vivo effects of IGF-I on the number of CFU-F/ALP+, bone marrow cells (BMCs) derived from normal mice, growth hormone (GH)-deficient lit/lit mice, or ovariectomized (OVX) mice were cultured and the CFU-F/ALP+ number was counted. Ex vivo treatment of IGF-I increased the CFU-F/ALP+ number in a dose-dependent manner compared with vehicle-treated control cultures. The CFU-F/ALP+ number was decreased by 20% (p < 0.01; n = 7-9) in GH-deficient lit/lit mice compared with age-matched control mice. Four weeks after OVX or sham operation, IGF-I (2 microg/g body wt) or vehicle was administered twice on day 1, and 5 days later, BMCs were removed from the femur and cultured for 10 days (n = 9-10 per group). IGF-I administration increased the CFU-F/ALP+ number by 63% (p < 0.01) and 19% (NS), respectively, in sham-operated (sham) and OVX mice compared with the vehicle-treated control group. The serum IGF-I level was similar in OVX mice compared with sham mice; this finding is different from that found in rats in which OVX increases the serum IGF-I level. This study showed that IGF-I is an important regulator of osteoblast-progenitor number in the BMCs of mice both ex vivo and in vivo and that the IGF-I response to increase the number of osteoblast progenitors was impaired in OVX mice.

Alkaline Phosphatase↗