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Biomedical subjects

Kiminori Yukata

Publications and source records attributed to Kiminori Yukata.

10 recordsLinked to original sources
PubMed2007

Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis.

The objective of this study is to examine the differential expression of mast cell tryptase and its receptor, protease-activated receptor-2 (PAR-2), in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Biochemical and immunohistochemical analyses were performed to determine whether the trypsin-like protease in the synovium is identical to mast cell tryptase. The effects of mast cell tryptase on the proliferation of synovial fibroblast-like cells (SFCs) and the release of IL-8 thereof were evaluated by the [3H]-thymidine incorporation and ELISA, respectively. The trypsin-like protease in the synovium of RA patients was identical to human mast cell tryptase, which was composed of two subunits: 33 and 34 kDa. The 33- and 34-kDa proteins are different glycosylated forms of the 31-kDa protein, which was unglycosylated. Mast cell tryptase activity in RA synovial fluid was significantly higher than that in OA synovial fluid, while their activities and expression in the synovium were similar. Expression of PAR-2 mRNA in the synovium was higher in RA than in OA. Mast cell tryptase containing the unglycosylated 31-kDa subunit was the predominant form in synovial fluid. RA patients had higher amounts of this subunit in their synovial fluid than OA patients. Mast cell tryptase and PAR-2 activating peptide stimulated the proliferation of SFCs and release of IL-8 from these cells. Mast cell tryptase secretion into RA synovial fluid is higher than OA synovial fluid. Mast cell tryptase in synovial fluid stimulates the proliferation of SFCs and the release of pro-inflammatory cytokines via PAR-2, which may contribute to exacerbation of synovitis in RA.

Adult↗
PubMed2006

Bisphosphonate modulates morphological and mechanical properties in distraction osteogenesis through inhibition of bone resorption.

Despite the general clinical acceptance of distraction osteogenesis and much attention to bone formation in this method, little is recognized about activated bone resorption in the regenerated bone. The purpose of this study was to demonstrate the simultaneously activated bone resorption with activated bone formation and to investigate the role and efficacy of bisphosphonate in distraction osteogenesis. Left tibiae of 54 immature rabbits were lengthened for 3 weeks at a rate of 0.7 mm/day after a 1-week lag. Regenerated bone was quantitatively investigated by radiographic bone density, bone histomorphometry, and three-point bending testing. Animals received either vehicle or nitrogen-containing bisphosphonate (N-BP), YM529/ONO5920 at doses of 0.4 mg/kg/w or 0.004 mg/kg/w for 6 weeks. Regenerated bone of the vehicle group showed a radiologically characteristic zone structure containing the osteopenic zones adjacent to the sclerotic zones. The regenerated bone of the 0.4-mg/kg/w group showed no osteopenic zones during the course and eventually became homogeneously radiodense. The bone volume corresponding to the osteopenic zone of this group was 5.6-fold greater compared with that of the vehicle group. The lengthened bone strength of this group was 3.3-fold greater in ultimate force than that of the vehicle group and equivalent to the contralateral tibia. The 0.004-mg/kg/w group had no substantial differences compared with the vehicle group, despite radiological enhancement of the mineralized front as well as somewhat delayed bone resorption. These results demonstrate that not only bone formation but also bone resorption is highly activated in the regenerated bone, implying high bone turnover. Sufficient N-BP caused a notable modulation in morphological properties of the regenerated bone through inhibition of highly activated bone resorption and eventually increased mechanical properties.

Absorptiometry, Photon↗
PubMed2006

Sp1 family of transcription factors regulates the human alpha2 (XI) collagen gene (COL11A2) in Saos-2 osteoblastic cells.

UNLABELLED: Genes encoding type XI collagen, normally associated with chondrogenesis, are also expressed by osteoblasts. By studying Saos-2 cells, we showed that the transcription factors, Sp1, Sp3, and Sp7 (Osterix), regulate COL11A2 expression through its proximal promoter. The findings indicate both ubiquitous and osteoblast-specific mechanisms of collagen gene regulation. INTRODUCTION: Type XI collagen is essential for skeletal morphogenesis. Collagen XI gene regulation has been studied in chondrocytes but not in osteoblasts. MATERIALS AND METHODS: We cultured Saos-2 cells, a human osteosarcoma-derived line of osteoblasts, and analyzed them for alpha2(XI) protein and COL11A2 regulatory mechanisms. RESULTS AND CONCLUSIONS: Although types I and V were the dominant collagens deposited by Saos-2 cells, they expressed COL11A2 mRNA, and alpha2(XI) chains were present in the extracellular matrix. The COL11A2 promoter region (from -149 to -40) containing three Sp1 binding sites was required for promoter activity in transient transfection assays. All three Sp1 sites were critical for binding by nuclear proteins in electrophoretic mobility shift assays. Further analysis using consensus oligonucleotides and specific antibodies as well as chromatin immunoprecipitation assay implicated Sp1 and Sp3 in binding to this promoter region. Overexpressing Sp1 or Sp3 significantly increased COL11A2 promoter activity and endogenous COL11A2 gene expression, an effect that was suppressed by the Sp1-binding inhibitor mithramycin A. Further experiments showed that Sp1, Sp3, CREB-binding protein (CBP), p300, and histone deacetylase (HDAC) were physically associated and HDAC inhibitors (trichostatin A or NaB) upregulated COL11A2 promoter activity and endogenous gene expression. Another Sp1 family member, Sp7 (Osterix), was expressed in Saos-2 cells, but not in chondrocytes, and was shown by chromatin immunoprecipitation to occupy the COL11A2 promoter. Overexpressing Sp7 increased COL11A2 promoter activity and endogenous gene expression, an effect also blocked by mithramycin A. Using siRNA to knockdown Sp1, Sp3, or Sp7, it was shown that depression of any of them decreased COL11A2 promoter activity and endogenous gene expression. Finally, primary cultures of osteoblasts expressed COL11A2 and Sp7, upregulated COL11A2 promoter activity and endogenous gene expression when Sp1, Sp3, or Sp7 were overexpressed, and downregulated them when Sp1, Sp3, or Sp7 were selectively depressed. The results establish that Sp1 proteins regulate COL11A2 transcription by binding to its proximal promoter and directly interacting with CBP, p300, and HDAC.

Base Sequence↗
PubMed2005

Overexpression of HMGA2-LPP fusion transcripts promotes expression of the alpha 2 type XI collagen gene.

In a subset of human lipomas, a specific t(3;12) chromosome translocation gives rise to HMGA2-LPP fusion protein, containing the amino (N)-terminal DNA binding domains of HMGA2 fused to the carboxyl (C)-terminal LIM domains of LPP. In addition to its role in adipogenesis, several observations suggest that HMGA2-LPP is linked to chondrogenesis. Here, we analyzed whether HMGA2-LPP promotes chondrogenic differentiation, a marker of which is transactivation of the alpha 2 type XI collagen gene (Col11a2). Real-time PCR analysis showed that HMGA2-LPP and COL11A2 were co-expressed. Luciferase assay demonstrated that either of HMGA2-LPP, wild-type HMGA2 or the N-terminal HMGA2 transactivated the Col11a2 promoter in HeLa cells, while the C-terminal LPP did not. RT-PCR analysis revealed that HMGA2-LPP transcripts in lipomas with the fusion were 591-fold of full-length HMGA2 transcripts in lipomas without the fusion. These results indicate that in vivo overexpression of HMGA2-LPP promotes chondrogenesis by upregulating cartilage-specific collagen gene expression through the N-terminal DNA binding domains.

Binding Sites↗
PubMed2005

Asynchronous progressive diaphyseal dysplasia.

We report the case of a 42-year-old Japanese woman with unusual diaphyseal dysplasia of bilateral femora. Radiographs showed thickening and sclerosis of the cortex with resultant enlargement of the diaphysis, unclear demarcation of the surface of the cortex, and no periosteal reaction. These changes were found on the left femur at the first presentation, and those on the right femur developed within several years. Although this patient partly presented characteristics of Ribbing disease and Camurati-Engelmann disease, the focal involvement of bilateral femora suggested an unknown pathogenesis.

Journal Article↗
PubMed2004

Influence of age on scapulo-thoracic orientation.

BACKGROUND: Scapular activity during shoulder motion is critical for normal shoulder function. With aging, muscle function deteriorates in almost all people, which may lead to shoulder impingement syndrome. METHODS: Forty-four normal subjects, 23 men and 21 women aged from 16 to 73 years with a mean age 48, were enrolled in the study. Static antero-posterior radiography at both 0 degrees and 90 degrees of abduction were undertaken and correlation between age and scapular orientations were evaluated by Pearson's correlation coefficient test. The purpose of this study is to investigate the relationship between aging and scapulo-thoracic orientation. FINDINGS: Significant correlation coefficients were observed between aging and scapular orientations. With the shoulder at 0 degrees abduction, posterior tilt showed significant negative correlation with aging. At 90 degrees abduction, both posterior tilt and upward rotation angle correlated negatively with aging. The correlation was apparent at 90 degrees abduction. INTERPRETATION: The results indicate that shoulder aging closely relates to changes of scapular orientation, which consist of decreases of the posterior tilt at 0 degrees and 90 degrees abduction and the upward rotation angle at 90 degrees. The current study indicated that one of the effects of aging on the shoulder is a decrease of posterior tilt and upward rotation angle as seen in an abducted position; and that these alterations are similar to the scapular kinematics of shoulder impingement syndrome. By taking this concept into consideration, the effects of aging on shoulder kinematics can be appropriately evaluated.

Adolescent↗
PubMedDate not supplied

Differential expression of VEGF isoforms and VEGF receptors in cartilaginous tumors.

Vascular endothelial growth factor (VEGF), which is known to have at least five isoforms and four receptors, is integral to tumor-induced neovascularization. In order to determine whether VEGF signaling is modulated in the development of cartilaginous tumors, we analyzed osteochondrogenic tumors for the expression of VEGF isoforms and VEGF receptors using the reverse transcription-polymerase chain reaction method. Although mRNA for VEGF121, VEGF165, VEGFR-1 and NRP-2 was widely expressed, mRNA expression for VEGF189, VEGFR-2 and NRP-1 was linked to a malignant phenotype such as local invasion. These results indicated that VEGF signaling was fine-tuned by the differential expression of the VEGF isoforms and VEGF receptors.

Bone Neoplasms↗
PubMedDate not supplied

MRI characteristics of parosteal lipomas associated with the HMGA2-LPP fusion gene.

BACKGROUND: The magnetic resonance (MR) characteristics of parosteal lipomas with the HMGA2-LPP fusion transcripts are described. PATIENTS AND METHODS: The expression of HMGA2-LPP fusion transcripts was determined using the reverse transcription-polymerase chain reaction method. RESULTS: MR images of two cases with the fusion transcripts, a 56-year-old man and a 50-year-old woman, revealed heterogeneous high signal intensities on T1- and T2-weighted images, showing heterogeneous curvilinear enhancement on fat-suppressed T1-weighted images after Gd-DTPA injection, which resembled those of well-differentiated liposarcomas. CONCLUSION: Since the HMGA2-LPP fusion transcripts are exclusively detectable in benign mesenchymal tumors, testing HMGA2-LPP expression may be useful for differential diagnosis in cases of radiologically-suspected well-differentiated liposarcomas.

Female↗