Histological evaluation for "bone quality" on two mouse models with different bone remodeling.
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Animals↗
Biomedical subjects
Junko Shimomura
Publications and source records attributed to Junko Shimomura.
Anterior crossbite in the primary dentition: proposal for a new analytical method in children.
The aim of this study was to clarify the features of profiles of patients with anterior crossbite in early childhood, using a new method of analysis. Lateral cephalograms of 139 (68 males; 71 females) untreated child patients with anterior crossbite in the primary dentition were assessed. The patients were aged from 3 to 5 years. To evaluate disharmony between the maxilla and the mandible, a proprietary calculating system, the Theoretical Individualized Profile drawing System (TIPS), was applied. Using this system, individualized standard cephalometric values were obtained for normal occlusion. This standard profile, which was harmonized with the cranial base structure of each patient, was compared with the child's original profile. The sizes of the mandibles in the children with anterior crossbite, subclassified into three age groups (3, 4, and 5 years) were greater, both horizontally and vertically, than those in the mean profiles derived from TIPS. The vertical size of the maxilla was smaller than that derived from TIPS in the patients aged 3 years. In contrast, in the patients aged 5 years, the vertical size of the maxilla was larger than that derived from TIPS. These results suggest that, in children with anterior crossbite, the vertical growth of the maxilla is closely related to the variation of morphological conditions with development.
Age Factors↗
Cell-cell interaction mediated by cadherin-11 directly regulates the differentiation of mesenchymal cells into the cells of the osteo-lineage and the chondro-lineage.
UNLABELLED: We studied cadherin-11 function in the differentiation of mesenchymal cells. Teratomas harboring the cadherin-11 gene generated bone and cartilage preferentially. Cadherin-11 transfectants of C2C12 cells and cadherin-11 and/or N-cadherin transfectants of L cells showed that cadherin-11 together with N-cadherin-induced expression of ALP and FGF receptor 2. These results suggest that cadherin-11 directly regulates the differentiation of mesenchymal cells into the cells of the osteo-lineage and the chondro-lineage in a different manner from N-cadherin. INTRODUCTION: Cell-cell interaction is an essential event for tissue formation; however, the role of cell-cell adhesion in mesenchymal tissue formation as well as in cell differentiation in this tissue remains unclear. cadherins, which are calcium-dependent cell adhesion receptors, form adherence junctions after adherence and aggregation of cells. Because cadherin-11 as well as N-cadherin has been reported to be a mesenchyme-related cadherin, we examined the cadherin-11 action in teratomas and in the cell lines C2C12 and L cell. Herein, we show that cell-cell interaction mediated by cadherin-11 is responsible for bone and cartilage formation. MATERIALS AND METHODS: It has been previously reported that N-cadherin-expressing E-cadherin-/- ES transfectants formed neuroepithelium and cartilage in teratomas. Thus, we transfected the E-cadherin-/- ES cell line with the cadherin-11 gene. Moreover, we also transfected C2C12 cells and L cells with the cadherin-11 gene for morphological analysis and study of the induced differentiation at the molecular level. RESULTS AND CONCLUSION: Teratomas derived from embryonic stem cells in which the cadherin-11 gene had been expressed exogenously contained bone and cartilage preferentially, showing that cadherin-11 is involved in mesenchymal tissue formation, specifically in controlling the differentiation of these cells into osteoblasts and chondrocytes. Therefore, we further examined the functional difference between cadherin-11 and N-cadherin. The expression patterns of cadherin-11 and N-cadherin in cells of the mouse osteoblastic cell line MC3T3-E1 showed that each cadherin was located independently of the cell-cell adhesion site and acted individually. In hanging drop cultures, cadherin-11 L cell transfectants aggregated in a sheet-like structure, whereas N-cadherin transfectants aggregated in a spherical form, indicating that each cadherin confers a different 3D architecture because of its individual adhesive property. To investigate the molecular mechanism of cadherin-11 action in cell differentiation, we analyzed cadherin-11 transfectants of C2C12 cells and cadherin-11 and/or N-cadherin transfectants of L cells and showed that cadherin-11, together with N-cadherin, induced expression of alkaline phosphatase (ALP) and fibroblast growth factor receptor 2. These results suggest that cadherin-11 directly regulates the differentiation of mesenchymal cells into the cells of the osteo-lineage and the chondro-lineage in a different manner from N-cadherin.
3T3 Cells↗
Tensile stress induces alpha-adaptin C production in mouse calvariae in an organ culture: possible involvement of endocytosis in mechanical stress-stimulated osteoblast differentiation.
We previously demonstrated that tensile stress (TS)-induced osteoblast differentiation eventually led to osteogenesis in an organ culture of mouse calvarial sutures. In the present study, we employed RNA-fingerprinting using an arbitrarily primed polymerase chain reaction (RAP-PCR) to identify alpha-adaptin C, a component of the endocytosis machinery AP2, as a TS-inducible gene. Protein production, as well as the gene expression of alpha-adaptin C, was induced by TS as early as 3 h following the initiation of loading. In situ hybridization and immunohistochemical analysis revealed that the induction of alpha-adaptin C mostly occurred in fibroblastic cells in the sutures, suggesting that it precedes TS-induced osteoblast differentiation. Consistent with this result, TS significantly increased the number of coated pits (CPs) and coated vesicles (CVs) in the undifferentiated fibroblastic cells but not in the osteoblastic cells around calvarial bones. Further, TS-induced osteoblast differentiation was suppressed when endocytosis was inhibited by potassium depletion. These results, taken together, suggest that TS accelerates osteoblast differentiation and osteogenesis, possibly through the induction of the alpha-adaptin C expression and consequent activation of receptor-mediated endocytosis.
Adaptor Protein Complex 2↗
Defective bone remodelling in osteoprotegerin-deficient mice.
Previous studies have reported enhanced osteoclastogenesis, increased bone resorption and osteoporosis in osteoprotegerin (OPG)-deficient mice. In the present study, we show that the tibial epiphyses contain abundant, thin trabeculae lined with numerous osteoclasts and cuboidal osteoblasts. The increase in osteoblasts and osteoclasts was associated with a dramatic increase in calcein labelling of the mineralization fronts and replacement of much of the intertrabecular marrow with numerous alkaline phosphatase-positive preosteoblasts. Furthermore, the discrete, linear cement lines seen in wild-type mice were replaced by a randomly oriented meshwork of cement lines that were stained intensely for tartrate-resistant acid phosphatase and osteopontin in the OPG-/- mice. These indices of accelerated bone remodelling in mutant bone were associated with irregular trabecular surfaces, a disorganized collagen matrix interspersed with amorphous ground substance and numerous fissures between old and new bone. In total, these observations indicate that enhanced osteoclastic activity in OPG-/- epiphyses led to a coupled increase in osteoblast differentiation and activity and an increase in bone remodelling. The high bone turnover, disorganized matrix and impaired attachment of new to old bone in the cement lines in OPG-/- mice appear to cause bone fragility.
Animals↗
[Mineralization and vascular invasion during endochondral bone formation].
The epiphyseal cartilage is composed of the distinct zones of resting, proliferative and hypertrophic chondrocytes. The intercolumnar cartilage matrix of the hypertrophic zone is subjected to mineralization whereas the transverse partitions of the cartilage column are poorly mineralized. Therefore, mineralized cartilage matrices are formed parallel to the longitudinal axis of the epiphyseal cartilage. Vascular endothelial cells invade the cartilage by penetrating the poorly mineralized transverse partition at the chondro-osseous junction, resulting in the exposure of mineralized intercolumnar matrix to bony tissue. The exposed mineralized cartilage matrices appear to serve as scaffolds for osteoblastic attachment. These osteoblasts deposit bone matrices onto the cartilage cores, forming primary trabecular bones. Vascular endothelial growth factor, VEGF, is a strong angiogenic factor, and play a pivotal role in vascular invasion into cartilage. The invading endothelial cells possess the receptor for VEGF, and secret matrix metallo protatenase to digest the cartilage matrices of the unmineralized transverse partition of the column.
English Abstract↗
Biological action of parathyroid hormone (PTH)-related peptide (PTHrP) mediated either by the PTH/PTHrP receptor or the nucleolar translocation in chondrocytes.
Parathyroid hormone (PTH)-related peptide (PTHrP) has been believed to act by binding the common receptor to PTH (PTH/PTHrP receptor). However, PTHrP is localized not only in the secretory pathway, but also in nucleoli by virtue of its nucleolar targeting signal (NTS). This review demonstrates the bipartite action of PTHrP on chondrocytes, the receptor-mediated and -independent signaling pathway. Mice with deletion of the PTHrP gene were characterized by a chondrodysplasia due to markedly reduced proliferation of epiphyseal chondrocytes. The PTH/PTHrP receptor was localized mainly in proliferative chondrocytes in the epiphyseal cartilage, indicating that PTHrP modulates normal proliferation via the receptor. In contrast to the receptor-mediated action, the mid-region of the amino acid sequence of PTHrP contains an NTS. The PTHrP-translation was found to initiate from both methionine-coding AUG and downstream leucine-coding CUGs in its signal sequence. When translated from CUGs, PTHrP accumulated in the nucleoli, and the translation from AUG localized PTHrP in both the Golgi apparatus and nucleoli. Therefore, nucleolar PTHrP appears to be derived from the translation initiating from both AUG and CUGs. A chondrocytic cell line expressing a full-length PTHrP, but not PTHrP lacking NTS, were resistant to apoptosis caused by serum depletion, suggesting that the nucleolar PTHrP in chondrocytes serves as a survival factor against apoptosis. Thus, PTHrP regulates chondrocyte proliferation, differentiation and apoptosis by mediating its receptor or acting directly on the nucleolus.
Animals↗