Differentiation of Hypertrophic Chondrocytes from Human iPSCs for the In Vitro Modeling of Chondrodysplasias.

Chondrodysplasias are hereditary diseases caused by mutations in the components of growth cartilage. Although the unfolded protein response (UPR) has been identified as a key disease mechanism in mouse models, no suitable in vitro system has been reported to analyze the pathology in humans. Here, we developed a three-dimensional culture protocol to differentiate hypertrophic chondrocytes from induced pluripotent stem cells (iPSCs) and examine the phenotype caused by MATN3 and COL10A1 mutations.

In vitro bone-like nodules generated from patient-derived iPSCs recapitulate pathological bone phenotypes.

The recapitulation of bone formation via the in vitro generation of bone-like nodules is frequently used to understand bone development. However, current bone-induction techniques are slow and difficult to reproduce. Here, we report the formation of bone-like nodules within ten days, via the use of retinoic acid (RA) to induce the osteogenic differentiation of human induced pluripotent stem cells (hiPSCs) into osteoblast-like and osteocyte-like cells that create human bone tissue when implanted in calvarial defects in mice.

The prevalence of the complications and their associated factors in humeral lengthening for achondroplasia: retrospective study of 54 cases.

The aim of this study is to evaluate the complications of humeral lengthening and their associated factors. Fifty-four achondroplastic patients were treated by bilateral humeral lengthening. Our original shoulder sling was sufficient to prevent shoulder dislocation.

1.0 s Ultrafast MRI in non-sedated infants after reduction with spica casting for developmental dysplasia of the hip: a feasibility study.

Purpose: The aim of this study was to first develop and use 1.0 s ultrafast magnetic resonance imaging (MRI) to confirm the location of the femoral head in non-sedated infants with developmental dysplasia of the hip (DDH) after reduction with spica cast application in clinical settings.

Methods: The ultrafast acquisition was achieved by employing a balanced steady-state free precession sequence and immobilizing the patient with dedicated sandbags.

CINCA syndrome with surgical intervention for valgus deformity and flexion contracture of the knee joint: A case report.

Chronic infantile neurological, cutaneous, and articular (CINCA) syndrome is a systemic autoinflammatory disease caused by increased production of interleukin (IL)-1β. We present a case of CINCA syndrome followed up to skeletal maturity. Joint contracture and valgus deformity of the knee had developed before diagnosis.

Femoral head volume indicates the severity of developmental dysplasia of the hip by a method using three-dimensional magnetic resonance imaging.

The aims of this study were to quantify the femoral head volume (FHV) in developmental dysplasia of the hip (DDH) and to estimate its relation with the severity of the disease. Fifty-one patients (age range 2-11 months) with unilateral DDH were evaluated using three-dimensional MRI. The relation among FHV, age, severity, and displacement was investigated.

Visualization of developmental dysplasia of the hip in infants by using three-dimensional magnetic resonance imaging.

Developmental dysplasia of the hip (DDH) includes various abnormalities such as instability, subluxation, and dislocation. In selecting the appropriate treatment method, it is important to distinguish these abnormalities from each other. We developed a novel approach for diagnosing DDH using three-dimensional MRI, which are used to visualize the spatial relation between the dislocated femoral head and the acetabulum and to clarify the changes during hip joint movement.

Histone modifiers, YY1 and p300, regulate the expression of cartilage-specific gene, chondromodulin-I, in mesenchymal stem cells.

Elucidating the regulatory mechanism for tissue-specific gene expression is key to understanding the differentiation process. The chondromodulin-I gene (ChM-I) is a cartilage-specific gene, the expression of which is regulated by the transcription factor, Sp3. The binding of Sp3 to the core-promoter region is regulated by the methylation status of the Sp3-binding motif as we reported previously.

A novel method to isolate mesenchymal stem cells from bone marrow in a closed system using a device made by nonwoven fabric.

Bone marrow stromal cells (BMSCs) include cells with multidirectional differentiation potential described as mesenchymal stem cells. For clinical use, it is important to develop a way to isolate BMSCs from bone marrow in a closed system without centrifugation. After screening 200 biomaterials, we developed a device containing a nonwoven fabric filter composed of rayon and polyethylene.

Expression of vascular cell adhesion molecule-1 indicates the differentiation potential of human bone marrow stromal cells.

Bone marrow stromal cells (BMSCs) are a mixture of cells differing in differentiation potential including mesenchymal stem cells, and so far no CD antigens were found to be predictable for the differentiation property of each BMSC. Here we attempted to isolate differentiation-associated CD antigens using 100 immortalized human BMSC (ihBMSC) clones. Among 13 CD antigens analyzed, only CD106/Vascular cell adhesion molecule-1 (VCAM-1) showed a clear correlation with the differentiation potential of each clone; CD106-positive ihBMSC clones were less osteogenic and more adipogenic than CD106-negative clones.

Cell-specific epigenetic regulation of ChM-I gene expression: crosstalk between DNA methylation and histone acetylation.

The expression of the chondromodulin-I (ChM-I) gene, a cartilage-specific gene, is regulated by the binding of Sp3 to the core promoter region, which is inhibited by the methylation of CpG in the target genome in the osteogenic lineage, osteosarcoma (OS) cells. The histone tails associated with the hypermethylated promoter region of the ChM-I gene were deacetylated by histone deacetylase 2 (HDAC2) in three ChM-I-negative OS cell lines. Treatment with an HDAC inhibitor induced the binding of Sp3 in one cell line, which became ChM-I-positive.

Expression of the p16INK4A gene is associated closely with senescence of human mesenchymal stem cells and is potentially silenced by DNA methylation during in vitro expansion.

The precise biological characteristics of human mesenchymal stem cells (hMSCs), including growth regulatory mechanisms, have not yet been defined. Using 29 strains of hMSCs isolated from bone marrow, we have performed extensive analyses of the growth profiles of hMSCs in vitro. All 29 strains stopped proliferating with a mean population doubling (PD) of 28, although there was a considerable difference among strains.

In vitro transformation of mesenchymal stem cells by oncogenic H-rasVal12.

Tissue stem cells may serve as progenitors for malignant tumors derived from the same tissue. Here, we report the establishment of immortalized human mesenchymal stem cells (ihMSC) and tested the feasibility of using ihMSC as presarcomatous cells. Immortalization was achieved by introducing the genes for human telomerase reverse transcriptase and Bmi1.

Expression of claudin7 is tightly associated with epithelial structures in synovial sarcomas and regulated by an Ets family transcription factor, ELF3.

Synovial sarcoma, a soft tissue sarcoma that develops in adults, is pathologically subclassified into monophasic spindle synovial sarcoma and biphasic synovial sarcoma with epithelial components. The molecular mechanism building the epithelial components in biphasic synovial sarcoma is totally unknown. Here we investigated claudins, critical molecules in the tight junction, in biphasic synovial sarcoma.

A modification of the retrograde medullary screw for the treatment of bilateral pubic ramus nonunions: a case report.

We describe a patient with bilateral pubic ramus nonunions who was treated successfully with a modification of the retrograde medullary screw technique, in which the screw orientation was altered so that it engaged the cancellous bone in the inferior part of the anterior column and the anterior-inferior cortex of the fossa acetabuli. The modification should be one option when the original technique is judged to be difficult to perform.