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Biomedical subjects

Muneaki Ishijima

Publications and source records attributed to Muneaki Ishijima.

9 recordsLinked to original sources
PubMed2006

Osteopontin is associated with nuclear factor kappaB gene expression during tail-suspension-induced bone loss.

Osteoporosis due to unloading-induced bone loss is a critical issue in the modern aging society. Although the mechanisms underlying this phenomenon are largely unknown, osteopontin (OPN) is one of the critical mediators required for unloading-induced bone loss [M. Ishijima, S.R. Rittling, T. Yamashita, K. Tsuji, H. Kurosawa, A. Nifuji, D.T. Denhardt, and M. Noda, Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin, J Exp Med, 193 (2001) 399-404]. To clarify the molecular bases for OPN actions, we carried out microarray analyses on the genes expressed in the femoral bone marrow cells in wild type and OPN-/- mice. The removal of the mechanical load induced bone loss in wild type, but not in OPN-/- mice, as previously reported. Expression analysis of 9586 cDNAs on a microarray system revealed that OPN deficiency blocked tail-suspension-induced expression of ten genes (group A). This observation was confirmed based on semi-quantitative RT-PCR analyses. On the other hand, expression of four genes (group B) was not altered by tail suspension in wild type but was enhanced in OPN-deficient mice. NF-kappaB p105 subunit gene (Nfkb1) was found in group A and Bax in group B. p53 gene expression was upregulated by tail suspension in wild type mice, but it was no longer observed in OPN-/- mice. These data indicate that OPN acts to mediate mechanical stress signaling upstream to the genes encoding apoptosis-related molecules, and its action is associated with alteration of the genes.

Animals↗
PubMed2005

Analysis of the risk factors regarding anterior cruciate ligament reconstruction using multiple-looped semitendinosus tendon.

The purpose of this study was to investigate the risk factors regarding anterior cruciate ligament (ACL) reconstruction using autogenous semitendinosus tendon by subjective evaluation of the patients. We studied 63 patients who had been followed for 18 months or longer after surgery. They comprised 31 men and 32 women aged 15-45 (mean, 25.5) years. The patients were divided into two groups by subjective scores. Subjective clinical evaluation was performed using 100 mm visual analogue scale (VAS). In the high score group (group H), the VAS score was 80 mm or higher, and in the low score group (group L), the score was less than 80 mm. Forty three patients were in group H and 20 patients were in group L. The parameters examined were age, gender, sports activity level, preoperative period, complicated meniscus injury, articular cartilage status, graft tendon size, joint stability, and knee extension muscle strength. There were 26 men and 17 women in group H, and 5 men and 15 women in group L. There were significantly more women in group L (p<0.01). The mean preoperative period after injury was 23+/-38 months in group H, and was 52+/-67 months in group L (p<0.05). The average side-to-side differences in anterior laxity were 1.3+/-1.0 mm in group H and 2.2+/-1.6 mm in group L (p<0.01). There were no significant differences in other parameters between the two groups. In this study the risk factors for poor subjective outcome following hamstring ACL surgery was female gender and prolonged delay from injury to operation.

Adolescent↗
PubMed2003

Osteopontin deficiency induces parathyroid hormone enhancement of cortical bone formation.

Intermittent PTH treatment increases cancellous bone mass in osteoporosis patients; however, it reveals diverse effects on cortical bone mass. Underlying molecular mechanisms for anabolic PTH actions are largely unknown. Because PTH regulates expression of osteopontin (OPN) in osteoblasts, OPN could be one of the targets of PTH in bone. Therefore, we examined the role of OPN in the PTH actions in bone. Intermittent PTH treatment neither altered whole long-bone bone mineral density nor changed cortical bone mass in wild-type 129 mice, although it enhanced cancellous bone volume as reported previously. In contrast, OPN deficiency induced PTH enhancement of whole-bone bone mineral density as well as cortical bone mass. Strikingly, although PTH suppressed periosteal bone formation rate (BFR) and mineral apposition rate (MAR) in cortical bone in wild type, OPN deficiency induced PTH activation of periosteal BFR and MAR. In cancellous bone, OPN deficiency further enhanced PTH increase in BFR and MAR. Analysis on the cellular bases for these phenomena indicated that OPN deficiency augmented PTH enhancement in the increase in mineralized nodule formation in vitro. OPN deficiency did not alter the levels of PTH enhancement of the excretion of deoxypyridinoline in urine, the osteoclast number in vivo, and tartrate-resistant acid phosphatase-positive cell development in vitro. These observations indicated that OPN deficiency specifically induces PTH activation of periosteal bone formation in the cortical bone envelope.

Animals↗
PubMed2003

Osteopontin expression in osteoblasts and osteocytes during bone formation under mechanical stress in the calvarial suture in vivo.

UNLABELLED: To clarify the role of OPN in bone formation under mechanical stress, we examined the expression and the function of OPN in bone using an expansion force-induced osteogenesis model. Our results indicated that OPN expression was enhanced during the bone formation and that OPN would be one of the positive factors for the bone formation under mechanical stress. INTRODUCTION: Bone formation is known to be stimulated by mechanical stress; however, molecules involved in stress-dependent regulation of bone formation have not yet been fully characterized. Extracellular matrix proteins such as osteopontin (OPN) could play a role in mediation of the mechanical stress signal to osteoblasts. However, the function of OPN in bone formation under mechanical force is not known. Therefore, we examined the expression and the role of OPN in bone formation in vivo under tensile mechanical stress. MATERIALS AND METHODS: Sagittal sutures of mice were subjected to expansion mechanical stress by setting orthodontic spring wires, and OPN expression during bone formation within the suture gap was examined. RESULTS: Expansion of the sutures resulted in bone formation at the edges of the parietal bones within the sagittal suture. Immunohistochemical analysis revealed abundant accumulation of OPN protein in the matrix of newly formed bone on the inner edge of the parietal bone within the mechanically expanded sutures. Osteoblasts forming bone within the suture subjected to tensile stress also exhibited high levels of OPN protein expression. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicated that OPN mRNA expression was enhanced in wild-type calvariae subjected to expansion force compared with the control calvariae where dead spring wires were set without expansion stress. In addition, type I collagen mRNA was also expressed in the calvariae under the mechanical stimuli. To understand the function of OPN, sagittal sutures in OPN-deficient mice were subjected the expansion stress, and bone formation within the suture to fill the expanded gap was compared with that observed in wild-type mice. OPN deficiency reduced bone formation at the edge of the parietal bone in contact with the expanded suture gap. CONCLUSIONS: These observations revealed that OPN plays a pivotal role in bone formation under tensile mechanical stress.

Animals↗
PubMed2002

Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice.

Rheumatoid arthritis is one of the most critical diseases that impair the quality of life of patients, but its pathogenesis has not yet been fully understood. Osteopontin (OPN) is an extracellular matrix protein containing Arg-Gly-Asp (RGD) sequence, which interacts with alpha(v)beta3 integrins, promotes cell attachment, and cell migration and is expressed in both synovial cells and chondrocytes in rheumatoid arthritis; however, its functional relationship to arthritis has not been known. Therefore, we investigated the roles of OPN in the pathogenesis of inflammatory process in a rheumatoid arthritis model induced by a mixture of anti-type II collagen mAbs and lipopolysaccharide (mAbs/LPS). mAbs/LPS injection induced OPN expression in synovia as well as cartilage, and this expression was associated with joint swelling, destruction of the surface structures of the joint based on scanning electron microscopy, and loss of toluidine blue-positive proteoglycan content in the articular cartilage in wild-type mice. In contrast, OPN deficiency prevented the mice from such surface destruction, loss of proteoglycan in the articular joint cartilage, and swelling of the joints even when the mice were subjected to mAbs/LPS injection. Furthermore, mAbs/LPS injection in wild-type mice enhanced the levels of CD31-positive vessels in synovia and terminal deoxynucleotidyltransferase-mediated UTP end labeling-positive chondrocytes in the articular cartilage, whereas such angiogenesis as well as chondrocyte apoptosis was suppressed significantly in OPN-deficient mice. These results indicated that OPN plays a critical role in the destruction of joint cartilage in the rheumatoid arthritis model in mice via promotion of angiogenesis and induction of chondrocyte apoptosis.

Animals↗
PubMed2002

Resistance to unloading-induced three-dimensional bone loss in osteopontin-deficient mice.

Recent development in three-dimensional (3D) imaging of cancellous bone has made possible true 3D quantification of trabecular architecture. This provides a significant improvement in the measures available to study and understand the mechanical functions of cancellous bone. We recently reported that the presence of osteopontin (OPN) was required for the effects of mechanical stress on bone as OPN-null (OPN-/-) mice showed neither enhancement of bone resorption nor suppression of bone formation when they were subjected to unloading by tail suspension. However, in this previous study, morphological analyses were limited to two-dimensional (2D) evaluation. Although bone structure is 3D and thus stress effect should be evaluated based on 3D parameters, no such 3D morphological features underlying the phenomenon have been known. To elucidate the role of OPN in mediating mechanical stress effect based on true quantitative examination of bone, we evaluated 3D trabecular structures of hindlimb bones of OPN-/- mice after tail suspension. Tail suspension significantly reduced 3D parameters of bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and anisotropy and increased 3D parameters on trabecular separation (Tb.Sp) in wild-type mice. In contrast, these 3D parameters were not altered after tail suspension in OPN-/- mice. These data provided evidence that OPN is required for unloading-induced 3D bone loss.

Absorptiometry, Photon↗
PubMed2002

[Bone regeneration and Mesenchymal stem cells].

Bone marrow mesenchymal stem cells have been considered to differentiate into cells in bone, cartilage, tendon, muscle, and fat. Further analyses revealed that these cell also give rise to myocardial cells, oval cells and nerve cells, indicating high plasticity of these cells. Recent researches have been focused to utilize these cells to regenerate not only bone but also the life-maintaining major organs. As a cell source for the future regeneration of multiple organs, regeneration of the bone marrow is critical and thus studies on the process of bone marrow regeneration will benefit not only bone physiology field alone but also that of many other organs.

English Abstract↗
PubMed2002

[A gene involved in angiogenesis and bone -osteopontin].

Osteopontin is expressed in bone and stored in hard tissues while it promoted survival of endothelial cells and enhances angiogenesis towards bone in ectopic implantation experiments. As regulation of bone remodeling in osteoporosis and other metabolic bone diseases is an important issue and is influenced by the interaction between bone and vessels. Molecular mechanisms involved in the angiogenesis in bone should be further investigated.

English Abstract↗