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1.  Ten year results of transtrochanteric valgus osteotomy with or without the shelf procedure 
International Orthopaedics  2013;37(4):599-604.
Purpose
The purpose of this study was to examine retrospectively the effectiveness of Sugioka’s transtrochanteric valgus osteotomy (TVO) combined with the shelf procedure for patients who had advanced osteoarthritis (OA) of the hip with severe acetabular dysplasia.
Methods
Sixty-two hips in 61 patients were reviewed retrospectively between April 1993 and March 2009. Of these hips, 25 hips with the pre-operative acetabular head index (AHI) ≥ 60 % (single group) underwent a TVO, whereas the other 37 with AHI < 60 % (combined group) underwent a TVO combined with the shelf procedure.
Results
Using conversion to total hip arthroplasty as the endpoint, the Kaplan-Meier survival rates at ten years were calculated to be 85.5 % for the single group and 100 % for the combined group; there was a significant difference between the two groups (p < 0.05, log-rank test). Similarly, calculated using progressive OA as the endpoint, survival rates at ten years were 69.5 % and 89.3 % respectively; there was also a significant difference between the two groups (p < 0.05, log-rank test). In the single group, the latest radiographic evaluations of the patients with the pre-operative AHI ≥ 70 % were significantly better than those of the patients with the pre-operative AHI < 70 % (P < 0.05).
Conclusion
More satisfactory ten year results of TVO were obtained in cases that had a pre-operative AHI of ≥70 %, or where the shelf procedure was added. It is desirable that acetabuloplasty be added for patients with pre-operative AHI < 70 %.
doi:10.1007/s00264-013-1810-z
PMCID: PMC3609964  PMID: 23385609
2.  Patient Selection Criteria for Periacetabular Osteotomy or Rotational Acetabular Osteotomy 
Background
Hip dysplasia is the most common cause of secondary osteoarthritis (OA). Periacetabular osteotomy (PAO) or rotational acetabular osteotomy (RAO) has been used as a joint-preserving procedure. However, the patient selection criteria are not clearly defined.
Questions/purposes
Based on a systematic review, we identified reported patient selection criteria for PAO or RAO.
Methods
We performed a systematic review of RAO and 18 studies met our inclusion criteria. For the PAO, the systemic review performed by Clohisy et al. was used.
Where Are We Now?
For patients with symptomatic hip dysplasia, lateral center-edge angle less than 10° to 30°, radiographic pre- or early OA, mean age at the time of surgery of 18 to 45 years, and improvement in joint congruency on AP radiograph with hip abduction, radiographic deformity correction consistently improved hip function in all studies. Radiographic OA progression was noted in 5% to 33% at 3.2 to 20 years postoperatively. Clinical score and prevention of radiographic OA progression of patients 50 years or older or with advanced stage were worse in younger patients or those with early stage.
Where Do We Need to Go?
The key challenges are (1) preoperative evaluation of articular cartilage; (2) indication for older patients; (3) prevention of secondary femoroacetabular impingement; and (4) intraarticular treatment combined with PAO or RAO.
How Do We Get There?
Future prospective, longitudinal cohort studies need to determine optimal patient selection criteria, risk factors for clinical failure, optimal deformity correction parameters, and the role of adjunctive surgical procedures.
doi:10.1007/s11999-012-2516-z
PMCID: PMC3492602  PMID: 22895690
3.  Heme oxygenase-1 modulates degeneration of the intervertebral disc after puncture in Bach 1 deficient mice 
European Spine Journal  2012;21(9):1748-1757.
Purpose
Intervertebral disc degeneration is considered to be a major feature of low back pain. Furthermore, oxidative stress has been shown to be an important factor in degenerative diseases such as osteoarthritis and is considered a cause of intervertebral disc degeneration. The purpose of this study was to clarify the correlation between oxidative stress and intervertebral disc degeneration using Broad complex-Tramtrack-Bric-a-brac and cap‘n’collar homology 1 deficient (Bach 1−/−) mice which highly express heme oxygenase-1 (HO-1). HO-1 protects cells from oxidative stress.
Methods
Caudal discs of 12-week-old and 1-year-old mice were evaluated as age-related models. Each group and period, 5 mice (a total of 20 mice, a total of 20 discs) were evaluated as age-related model. C9–C10 caudal discs in 12-week-old Bach 1−/− and wild-type mice were punctured using a 29-gauge needle as annulus puncture model. Each group and period, 5 mice (a total of 60 mice, a total of 60 discs) were evaluated. The progress of disc degeneration was evaluated at pre-puncture, 1, 2, 4, 8 and 12 weeks post-puncture. Radiographic, histologic and immunohistologic analysis were performed to compare between Bach 1−/− and wild-type mice.
Results
In the age-related model, there were no significant differences between Bach 1−/− and wild-type mice radiologically and histologically. However, in the annulus puncture model, histological scoring revealed significant difference at 8 and 12 weeks post-puncture. The number of HO-1 positive cells was significantly greater in Bach 1−/− mice at every period. The apoptosis rate was significantly lower at 1 and 2 weeks post-puncture in Bach 1−/− mice.
Conclusions
Oxidative stress prevention may avoid the degenerative process of the intervertebral disc after puncture, reducing the number of apoptosis cells. High HO-1 expression may also inhibit oxidative stress and delay the process of intervertebral disc degeneration.
doi:10.1007/s00586-012-2442-5
PMCID: PMC3459108  PMID: 22832873
Intervertebral disc; Oxidative stress; Heme oxygenase-1; Intervertebral disc degeneration
4.  Autologous Bone-Marrow Mesenchymal Stem Cell Implantation and Endothelial Function in a Rabbit Ischemic Limb Model 
PLoS ONE  2013;8(7):e67739.
Background
The purpose of this study was to determine whether autologous mesenchymal stem cells (MSCs) implantation improves endothelial dysfunction in a rabbit ischemic limb model.
Methods
We evaluated the effect of MSC implantation on limb blood flow (LBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSCs were implanted (n = 20) or saline was injected as a control group (n = 20). LBF was measured using an electromagnetic flowmeter. A total of 106 MSCs were implanted into each ischemic limb.
Results
Histological sections of ischemic muscle showed that capillary index (capillary/muscle fiber) was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar.
Conclusions
These findings suggest that MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production.
doi:10.1371/journal.pone.0067739
PMCID: PMC3701528  PMID: 23861797
5.  Treatment of cartilage defects by subchondral drilling combined with covering with atelocollagen membrane induces osteogenesis in a rat model 
Background
The coverage of the atelocollagen membrane at the chondral defect after subchondral drilling might improve the beneficial effects for cartilage repair because of the prevention of scattering and accumulation of cells and growth factors from bone marrow within the chondral defect. On the other hand, it might block cells and factors derived from the synovium or cause high pressure in the chondral defect, resulting in prevention of cells and growth factors gushing out from the bone marrow, which leads to disadvantages for cartilage repair.
Method
We tested this hypothesis in a 2-mm-diameter chondral defect created in the articular cartilage of the patellar groove in a rat models. Defects were left untreated, or were drilled or drilled and covered with an atelocollagen membrane; healing was evaluated by histology and gene expression analysis using real-time polymerase chain reaction and immunohistochemistry.
Results
Membrane coverage induced bone tissue ingrowth into the punched chondral defect. At 1 week, expression of TGFβ, Sox9, Runx2, osteocalcin, Col1a1, and Col2a1 in the drilling group was significantly higher than in the covering group. At 4 weeks, expressions of TGFβ, Runx2, and Col1a1 were all significantly higher in the drilling group, while Sox9, osteocalcin, and Col2a1 were significantly higher in the covering group. Immunohistochemistry demonstrated Sox9, osteocalcin, and type II collagen on the bony reparative tissue in the covering group.
Conclusions
These results suggest that the atelocollagen membrane coverage resulted in inhibition of cartilage repair.
doi:10.1007/s00776-013-0379-0
PMCID: PMC3726928  PMID: 23564076
6.  The 86th Annual Meeting of the Japanese Orthopaedic Association 
Journal of Orthopaedic Science  2013;18(2):193-196.
doi:10.1007/s00776-013-0375-4
PMCID: PMC3608868  PMID: 23479205
8.  Mid-term results of acetabular reconstruction using a Kerboull-type acetabular reinforcement device 
International Orthopaedics  2011;36(1):23-26.
Purpose
The purpose of this study was to investigate the mid-term results of 32 acetabular reconstructions performed using a Kerboull-type acetabular reinforcement device and bone graft between June 1997 and January 2009.
Methods
The mean age of the patients at the time of surgery was 71.4 years (range 55–85). Patients were followed-up for a mean of 7.5 years (range 2.1–13.7). The acetabular bone defects according to the American Academy of Orthopaedic Surgeons system was type III for 29 hips and type IV for three hips. Bulk allografts were performed in 30 hips and morselised autografts (iliac bone) were performed in two hips. Clinical evaluations were made according to the criteria of Postel/Merle d’Aubigné.
Results
The mean pre-operative Postel/Merle d’Aubigné hip score was 7.0±2.9, and the final follow-up hip score was 12.6±2.8. Six hips showed radiographic loosening, and two hips required further revision. A Kaplan-Meier analysis showed that the five-year and ten-year survival rates were 96.9% and 92.3%, respectively, using further revision of the acetabular device as an end point.
Conclusion
Acetabular reconstruction using a Kerboull-type acetabular reinforcement device and bone graft gives satisfactory mid-term results.
doi:10.1007/s00264-011-1248-0
PMCID: PMC3251663  PMID: 21574052
9.  Diversity of angiogenesis among malignant bone tumors 
Molecular and Clinical Oncology  2012;1(1):131-136.
Several studies have demonstrated that angiogenesis assessed by microvessel density (MVD) correlates with patient prognosis in various types of cancer, whereas data regarding the relevance of angiogenesis and prognosis in malignant bone tumors are scarce and controversial. The aim of this study was to examine MVD in representative malignant bone tumors, such as osteosarcoma, chondrosarcoma and Ewing’s sarcoma, in order to clarify the role of angiogenesis in prognosis. A total of 69 patients with malignant bone tumors, including 44 osteosarcomas, 20 chondrosarcomas and 5 Ewing’s sarcomas, were reviewed retrospectively and treated at our hospital between 1980 and 2007. Biopsy or pre-chemotherapy surgical specimens were immunohistochemically stained with anti-CD34 antibody. The MVD values of osteosarcomas and Ewing’s sarcomas were significantly higher compared to chondrosarcoma. In osteosarcomas with high MVD, American Joint Committee on Cancer stage IIA, good histological response to chemotherapy was significantly correlated with better disease-free survival, while MVD was closely associated with age and chemotherapy response. In chondrosarcomas, the surgical margin (marginal and intralesional), MVD (high), tumor size (≥8) and histological grade (grades 2 and 3) significantly correlated with a shorter disease-free survival, while MVD was closely associated with age and histological grade. These findings showed that osteosarcomas and Ewing’s sarcomas were hypervascular, compared to chondrosarcomas. In osteosarcomas, hypervascularity induced good chemotherapy response, leading to better prognosis, while in chondrosarcomas, high MVD was associated with histological grade and predicted poor prognosis.
doi:10.3892/mco.2012.11
PMCID: PMC3956242  PMID: 24649135
angiogenesis; osteosarcoma; chondrosarcoma; Ewing’s sarcoma; prognosis
10.  Correlation between p38 mitogen-activated protein kinase and human telomerase reverse transcriptase in sarcomas 
Background
One of the major components of telomerase is the human telomerase reverse transcriptase (hTERT) as the catalytic protein. hTERT mRNA expression are reported to be associated with prognosis and tumor progression in several sarcomas. However, there is no clear understanding of the mechanisms of hTERT in human sarcomas. Recent studies have suggested that signals transmitted through p38 mitogen-activated protein kinase (MAPK) can increase or decrease hTERT transcription in human cells. The purpose of this study was to analyse the correlation between p38 MAPK and hTERT in sarcoma samples.
Methods
We investigated 36 soft tissue malignant fibrous histiocytomas (MFH), 24 liposarcomas (LS) and 9 bone MFH samples for hTERT and p38 MAPK expression. Quantitative detection of hTERT and p38 MAPK was performed by RT-PCR.
Results
There was a significant positive correlation between the values of hTERT and p38 MAPK in all samples (r = 0.445, p = 0.0001), soft tissue MFH (r = 0.352, p = 0.0352), LS (r = 0.704, p = 0.0001) and bone MFH samples (r = 0.802, p = 0.0093). Patients who had a higher than average expression of p38 MAPK had a significantly worse prognosis than other patients (p = 0.0036).
Conclusions
p38 MAPK may play a role in up-regulation of hTERT, and therefore, p38 MAPK may be a useful marker in the assessment of hTERT and patients' prognosis in sarcomas.
doi:10.1186/1756-9966-31-5
PMCID: PMC3296589  PMID: 22243975
p38 mitogen-activated protein kinase; human telomerase reverse transcriptase; malignant fibrous histiocytoma; liposarcoma
11.  Double bundle arthroscopic Anterior Cruciate Ligament reconstruction with remnant preserving technique using a hamstring autograft 
Background
Preservation of the Anterior Cruciate Ligament (ACL) remnant is important from the biological point of view as it enhances revascularization, and preserves the proprioceptive function of the graft construct. Additionally, it may have a useful biomechanical function. Double bundle ACL reconstruction has been shown to better replicate the native ACL anatomy and results in better restoration of the rotational stability than single bundle reconstruction.
Methods
We used the far anteromedial (FAM) portal for creation of the femoral tunnels, with a special technique for its preoperative localization using three dimensional (3D) CT. The central anteromedial (AM) portal was used to make a longitudinal slit in the ACL remnant to allow visualization of the tips of the guide pins during anatomical creation of the tibial tunnels within the native ACL tibial foot print. The use of curved hemostat allow retrieval of the wire loop from the apertures of the femoral tunnels through the longitudinal slit in the ACL remnant thereby, guarding against impingement of the reconstruction graft against the ACL remnant as well as the roof of the intercondylar notch.
Conclusion
Our technique allows for anatomical double bundle reconstruction of the ACL while maximally preserving the ACL remnant without the use of intra-operative image intensifier.
doi:10.1186/1758-2555-3-30
PMCID: PMC3284875  PMID: 22141394
12.  Shed Blood-derived Cells from Total Hip Arthroplasty Have Osteoinductive Potential: A Pilot Study 
Background
Cell therapy using autologous cells has been used in the treatment of various medical conditions. The mononuclear cell (MNC) fraction of bone marrow (BM) contains stem/progenitor cells that could contribute to osteogenesis and angiogenesis.
Questions/purposes
We asked whether MNCs derived from intraoperative shed blood (SB), consisting of peripheral blood and BM, have osteoinductive and angiogenic potential.
Methods
We harvested SB and BM from six patients undergoing THA. Isolated MNCs from SB and BM were analyzed by flow cytometry to evaluate the CD34+ cell fraction and 1 × 106 cells were seeded on an interconnective porous calcium hydroxyapatite ceramic (IP-CHA) and transplanted in the backs of athymic rats. IP-CHAs without cells were transplanted as controls and all composites were harvested after 4 and 8 weeks. Osteoinductive potential was evaluated by histologic observation, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) using anti-osteocalcin (OC) antibodies qualitatively and quantitatively. To evaluate angiogenic potential, capillary density was measured by immunohistochemistry using Isolectin B4 4 weeks after implantation.
Results
We found that CD34+ cells existed in SB-MNCs and there was a trend toward lower frequency compared with BM-MNCs. Histologic osteoinduction, OC expression, and capillary density were increased by transplantation of MNCs from SB. Similar results were achieved with MNCs from BM.
Conclusions
MNCs from SB have equivalent osteoinductive and angiogenic potential compared with those from BM.
Clinical Relevance
SB could be an attractive source for isolation of MNCs, enhancing osteoinduction and neovascularization, to augment the reconstruction of skeletal defects.
doi:10.1007/s11999-010-1444-z
PMCID: PMC3049633  PMID: 20585911
13.  Quantitative assessment of myelopathy patients using motor evoked potentials produced by transcranial magnetic stimulation 
European Spine Journal  2009;19(5):685-690.
Motor evoked potentials (MEPs) study using transcranial magnetic stimulation (TMS) may give a functional assessment of corticospinal conduction. But there are no large studies on MEPs using TMS in myelopathy patients. The purpose of this study is to confirm the usefulness of MEPs for the assessment of the myelopathy and to investigate the use of MEPs using TMS as a screening tool for myelopathy. We measured the MEPs of 831 patients with symptoms and signs suggestive of myelopathy using TMS. The MEPs from the abductor digiti minimi (ADM) and abductor hallucis (AH) muscles were evoked by transcranial magnetic brain stimulation. Central motor conduction time (CMCT) is calculated by subtracting the peripheral conduction time from the MEP latency. Later, 349 patients had surgery for myelopathy (operative group) and 482 patients were treated conservatively (nonoperative group). CMCTs in the operative group and nonoperative group were assessed. MEPs were prolonged in 711 patients (86%) and CMCTs were prolonged in 493 patients (59%) compared with the control patients. CMCTs from the ADM and AH in the operative group were significantly more prolonged than that in the nonoperative group. All patients in the operative group showed prolongation of MEPs or CMCTs or multiphase of the MEP wave. MEP abnormalities are useful for an electrophysiological evaluation of myelopathy patients. Moreover, MEPs may be effective parameters in spinal pathology for deciding the operative treatment.
doi:10.1007/s00586-009-1246-8
PMCID: PMC2899952  PMID: 20033461
Motor evoked potential; Transcranial magnetic stimulation; Central motor conduction time; Myelopathy; Diagnosis
14.  Stem/progenitor cells in closed suction drainage fluid after hip arthroplasty 
Acta Orthopaedica  2011;82(2):217-222.
Background and purpose
Drainage after surgery is commonly used, and the contents are generally discarded as clinical waste. We analyzed closed suction drainage fluid from hip arthroplasty patients to determine whether any multipotent stem cells were present that could be used as a source of cells for tissue regeneration.
Methods
Drainage fluid was obtained from 14 patients after hip arthroplasty on the day of surgery, the next day, and 2 days after surgery. Peripheral blood and bone marrow from the iliac crest were also obtained from the same patients during surgery. These samples were examined using regular flow cytometric profiling, and we performed quantitative immunoassays of stromal-derived factor-1 (SDF1) levels in the plasma. Mononuclear cells (MNCs) from these samples were also isolated and cultured. Fibroblastic adherent cells from MNC fractions were cultured in an osteogenic and a chondrogenic differentiation medium and were then evaluated for multipotentency.
Results and interpretation
Fibroblastic adherent cells were isolated from the mononuclear cell fraction of bone marrow and drainage fluid on the day of surgery, but they were not present in either the mononuclear cell fraction of the peripheral blood or the drainage fluid on the next day and 2 days after surgery. The cells from the drainage fluid on the day of surgery could differentiate in vitro into osteogenic and chondrogenic cells. SDF1 was elevated on the day of surgery, while CXCR4 was elevated on that day and the next day. This suggests that locally-induced SDF1 contributes to the mobilization of circulating CXCR4-positive cells. These results show that the drainage fluid collected on the day of surgery contains stem/progenitor cells that could be used for autologous cell-based therapy.
doi:10.3109/17453674.2011.566153
PMCID: PMC3235294  PMID: 21434846
15.  MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients 
Background
Interleukin (IL)-17 is an important factor in rheumatoid arthritis (RA) pathogenesis. MicroRNA (miRNA)s are a family of non coding RNAs and associated with human diseases including RA. The purpose of this study is to identify the miRNAs in the differentiation of IL-17 producing cells, and analyze their expression pattern in the peripheral blood mononuclear cells (PBMC) and synovium from RA patients.
Methods
IL-17 producing cells were expanded from CD4+T cell. MiRNA microarray was performed to identify the miRNAs in the differentiation of IL-17 producing cells. Quantitative polymerase chain reaction was performed to examine the expression patterns of the identified miRNAs in the PBMC and synovium from RA and osteoarthritis (OA) patients. Double staining combining in situ hybridization and immunohistochemistry of IL-17 was performed to analyze the expression pattern of identified miRNA in the synovium.
Results
Six miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells. The expression of miR-146a and IL-17 was higher than in PBMC in the patients with low score of Larsen grade and short disease duration. MiR-146a intensely expressed in RA synovium in comparison to OA. MiR-146a expressed intensely in the synovium with hyperplasia and high expression of IL-17 from the patients with high disease activity. Double staining revealed that miR-146a expressed in IL-17 expressing cells.
Conclusion
These results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients. There is the possibility that miR-146a participates in the IL-17 expression.
doi:10.1186/1471-2474-11-209
PMCID: PMC2950393  PMID: 20840794
16.  Lipophilic Bisphosphonates as Dual Farnesyl/Geranylgeranyl Diphosphate Synthase Inhibitors: An X-ray and NMR Investigation 
Considerable effort has focused on the development of selective protein farnesyl transferase (FTase) and protein geranylgeranyl transferase (GGTase) inhibitors as cancer chemotherapeutics. Here, we report a new strategy for anti-cancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Due to dual site targeting and decreased polarity, the compounds have activities far greater than do current bisphosphonate drugs in inhibiting tumor cell growth and invasiveness, both in vitro and in vivo. We explore how these compounds inhibit cell growth, how cell activity can be predicted based on enzyme inhibition data, and, using x-ray diffraction, solid state NMR and isothermal titration calorimetry, we show how these compounds bind to FPPS and/or GGPPS.
doi:10.1021/ja808285e
PMCID: PMC2753403  PMID: 19309137
17.  Intra-articular angiolipoma of the knee: a case report 
We report a case of intra-articular angiolipoma of the knee. This case report describes our experience in excising an intra-articular angiolipoma of the knee joint. Complete resection under arthroscopy was performed in a 30-year-old man. Two years after the surgery, no evidence of recurrence was seen. Intra-articular angiolipomas should be considered in the differential diagnosis of intra-articular masses in adolescents with recurrent hemarthrosis without trauma.
doi:10.1186/1758-2555-2-10
PMCID: PMC2861054  PMID: 20388202
18.  Expression of microRNA-146 in osteoarthritis cartilage 
Arthritis and rheumatism  2009;60(4):1035-1041.
Objective
A role of microRNAs, which are ∼22- nucleotide non coding RNAs, has recently been recognized in human diseases. The objective of this study was to identify the expression pattern of microRNA-146 (miR-146) in cartilage from patients with osteoarthritis (OA).
Methods
The expression of miR-146 in cartilage from 15 patients with OA was analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and by in situ hybridization. Induction of the expression of miR-146 by cultures of normal human articular chondrocytes following stimulation with interleukin-1β (IL-1β) was examined by quantitative RT-PCR.
Results
All cartilage samples were divided into three groups according to a modified Mankin scale; grade I: 0 - 5, grade II: 6 - 10, grade III: 11 - 14. In OA cartilage samples of grade I, the expression of miR-146a and Col2a1 was significantly higher than that of other groups (p<0.05). In OA cartilage of grades II and III, the expression of miR-146a and Col2a1 decreased while the expression of MMP13 was elevated in grade II. These data show that miR-146a is expressed intensely in cartilage with a low Mankin grade, and that miR-146a expression decreases in accordance with level of MMP13 expression. Section in situ hybridization of pri-miR-146a revealed that pri-miR-146a is expressed in chondrocytes in all layers, especially in the superficial layer where it is intensely expressed. The expression of miR-146 was markedly elevated by IL-1β stimulation in human chondrocytes in vitro.
Conclusion
This study shows that miR-146 is intensely expressed in low grade OA cartilage, and that its expression is induced by stimulation of IL-1β. MiR-146 might play a role in OA cartilage pathogenesis.
doi:10.1002/art.24404
PMCID: PMC2670476  PMID: 19333945
19.  The effect of an external magnetic force on cell adhesion and proliferation of magnetically labeled mesenchymal stem cells 
Background
As the strategy for tissue regeneration using mesenchymal stem cells (MSCs) for transplantation, it is necessary that MSCs be accumulated and kept in the target area. To accumulate MSCs effectively, we developed a novel technique for a magnetic targeting system with magnetically labeled MSCs and an external magnetic force. In this study, we examined the effect of an external magnetic force on magnetically labeled MSCs in terms of cell adhesion and proliferation.
Methods
Magnetically labeled MSCs were plated at the bottom of an insert under the influence of an external magnetic force for 1 hour. Then the inserts were turned upside down for between 1 and 24 hours, and the number of MSCs which had fallen from the membrane was counted. The gene expression of MSCs affected magnetic force was analyzed with microarray. In the control group, the same procedure was done without the external magnetic force.
Results
At 1 hour after the inserts were turned upside down, the average number of fallen MSCs in the magnetic group was significantly smaller than that in the control group, indicating enhanced cell adhesion. At 24 hours, the average number of fallen MSCs in the magnetic group was also significantly smaller than that in control group. In the magnetic group, integrin alpha2, alpha6, beta3 BP, intercellular adhesion molecule-2 (ICAM-2), platelet/endothelial cell adhesion molecule-1 (PECAM-1) were upregulated. At 1, 2 and 3 weeks after incubation, there was no statistical significant difference in the numbers of MSCs in the magnetic group and control group.
Conclusions
The results indicate that an external magnetic force for 1 hour enhances cell adhesion of MSCs. Moreover, there is no difference in cell proliferation after using an external magnetic force on magnetically labeled MSCs.
doi:10.1186/1758-2555-2-5
PMCID: PMC2828444  PMID: 20152029
20.  Liposarcoma Arising in the Foot: A Case Report 
Case Reports in Medicine  2009;2009:630203.
Liposarcoma is categorized as a soft tissue sarcoma and most commonly appears in the lower extremities and rarely in the foot during adulthood. We present a very rare case report of a primary well-differentiated liposarcoma arising in the foot on a 60-year-old female. Marginal resection of the tumor with metatarsal ray amputation was eventually performed. The patient's postoperative course was uneventful without recurrence 5 years after the original operation. The authors review the literature and also report on the low incidence of this tumor arising in the foot.
doi:10.1155/2009/630203
PMCID: PMC2774536  PMID: 19902014
21.  Expression of MicroRNA-146 in Rheumatoid Arthritis Synovial Tissue 
Arthritis and rheumatism  2008;58(5):1284-1292.
Objective
Several microRNA, which are ~22-nucleotide noncoding RNAs, exhibit tissue-specific or developmental stage–specific expression patterns and are associated with human diseases. The objective of this study was to identify the expression pattern of microRNA-146 (miR-146) in synovial tissue from patients with rheumatoid arthritis (RA).
Methods
The expression of miR-146 in synovial tissue from 5 patients with RA, 5 patients with osteoarthritis (OA), and 1 normal subject was analyzed by quantitative reverse transcription–polymerase chain reaction (RT-PCR) and by in situ hybridization and immunohistochemistry of tissue sections. Induction of miR-146 following stimulation with tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) of cultures of human rheumatoid arthritis synovial fibroblasts (RASFs) was examined by quantitative PCR and RT-PCR.
Results
Mature miR-146a and primary miR-146a/b were highly expressed in RA synovial tissue, which also expressed TNFα, but the 2 microRNA were less highly expressed in OA and normal synovial tissue. In situ hybridization showed primary miR-146a expression in cells of the superficial and sublining layers in synovial tissue from RA patients. Cells positive for miR-146a were primarily CD68+ macrophages, but included several CD3+ T cell subsets and CD79a+ B cells. Expression of miR-146a/b was markedly up-regulated in RASFs after stimulation with TNFα and IL-1β.
Conclusion
This study shows that miR-146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNFα and IL-1β. Further studies are required to elucidate the function of miR-146 in these tissues.
doi:10.1002/art.23429
PMCID: PMC2749927  PMID: 18438844
23.  Clinical application of scaffolds for cartilage tissue engineering 
The purpose of this paper is to review the basic science and clinical literature on scaffolds clinically available for the treatment of articular cartilage injuries. The use of tissue-engineered grafts based on scaffolds seems to be as effective as conventional ACI clinically. However, there is limited evidence that scaffold techniques result in homogeneous distribution of cells. Similarly, few studies exist on the maintenance of the chondrocyte phenotype in scaffolds. Both of which would be potential advantages over the first generation ACI. The mean clinical score in all of the clinical literature on scaffold techniques significantly improved compared with preoperative values. More than 80% of patients had an excellent or good outcome. None of the short- or mid-term clinical and histological results of these tissue-engineering techniques with scaffolds were reported to be better than conventional ACI. However, some studies suggest that these methods may reduce surgical time, morbidity, and risks of periosteal hypertrophy and post-operative adhesions. Based on the available literature, we were not able to rank the scaffolds available for clinical use. Firm recommendations on which cartilage repair procedure is to be preferred is currently not known on the basis of these studies. Randomized clinical trials and longer follow-up periods are needed for more widespread information regarding the clinical effectiveness of scaffold-based, tissue-engineered cartilage repair.
doi:10.1007/s00167-008-0663-2
PMCID: PMC2688024  PMID: 19020862
Articular cartilage; Tissue engineering; Scaffold; Autologous chondrocyte implantation; Matrix-induced autologous chondrocyte implantation
24.  Immunohistochemical expression of promyelocytic leukemia body in soft tissue sarcomas 
Background
The function of promyelocytic leukemia (PML) bodies is not well known but plays an important role in controlling cell proliferation, apoptosis and senescence. This study was undertaken to analyze the clinical significance of PML body expression in primary tumor samples from malignant fibrous histiocytoma (MFH) and liposarcoma patients.
Methods
We studied MFH and liposarcoma samples from 55 patients for PML bodies. Fluorescent immunostaining of PML bodies was performed in the paraffin-embedded tumor sections.
Results
PML body immunostaining was identified in 63.9% of MFH and 63.2% of liposarcoma samples. PML body expression rates of all sarcoma cells were 1.5 ± 1.8% (range: 0–7.0) in MFH and 1.3 ± 1.4% (0–5.2) in liposarcoma samples. PML body expression (p = 0.0053) and a high rate of PML body expression (p = 0.0012) were significantly greater prognostic risk factors for death than the other clinical factors in MFH patients. All liposarcoma patients without expression of PML were disease free at the end of the study.
Conclusion
Our study suggests that the presence of PML bodies may indicate a poor prognosis for MFH and liposarcoma patients.
doi:10.1186/1756-9966-27-73
PMCID: PMC2611968  PMID: 19025608
25.  Augmentation of tendon attachment to porous ceramics by bone marrow stromal cells in a rabbit model 
International Orthopaedics  2006;31(3):353-358.
Tendon attachment to interconnected porous calcium hydroxyapatite ceramics (IP-CHA) with cultured bone marrow stromal cells (BMSC) was analysed. The purpose of this study was to evaluate whether BMSC in IP-CHA could augment the tendon attachment to IP-CHA histologically and biomechanically. Eighteen Japanese white rabbits were used. Cultured BMSCs were subcultured in IP-CHA. The grafted tendon and IP-CHA with BMSC complex were implanted in a bone defect of the knee [BMSC(+) group]. In the contralateral knee, a tendon and IP-CHA without BMSC complex were implanted [BMSC(-) group]. Histological findings of the interface between the tendon and IP-CHA were similar in the two groups 3 weeks after the operation. However, 6 weeks after the operation, more abundant bone formation around the tendon was observed in the BMSC(+) group. The direct apposition of the tendon to bone in pores and collagen fibre continuity between the tendon and fibrous tissue in pores were observed. In biomechanical evaluation, the maximum pull-out load of the tendon from the IP-CHA in the BMSC(+) group was significantly higher than that in the BMSC(-) group 6 weeks after the operation. BMSCs cultured in IP-CHA could augment tendon attachment to IP-CHA.
doi:10.1007/s00264-006-0194-8
PMCID: PMC2267600  PMID: 16909253

Results 1-25 (28)