Collagen gene expression during chondrogenesis from chick periosteum-derived cells

AbstractChick periosteum-derived cells, which do not enter the chondrogenic cell lineage during normal bone development and growth, exhibit chondrogenic potential in high cell density culture conditions. In such cultures, collagen gene expression was temporally analyzed at the mRNA level by a reverse transcription PCR (RT-PCR) procedure, which showed that α1(II) and α1(IX) collagen mRNAs are coordinately increased, coincident with the onset of overt chondrogenesis, and subsequently decreased as chondrocytes exhibited hypertrophic characteristics. α1(X) collagen mRNA was detected well before the onset of chondrogenesis and markedly increased along with the hypertrophic change. For α2(I) collagen, both the bone/tendon form and the cartilage form of mRNA were detected throughout the culture period. This culture system provides an experimental vehicle capable of investigating the molecular events involved in the full range of chondrogenic differentiation starting from uncommitted periosteum-derived mesenchymal stem cells

Circumferential Spinal Cord Decompression through a Single Posterior Approach with Microendoscopy for Thoracic and Thoracolumbar Ossification of the Posterior Longitudinal Ligament

Thoracic and thoracolumbar ossification of the posterior longitudinal ligament (OPLL) can be difficult to treat due to the anatomical position. The purpose of this study was to report the significance of a novel surgical technique that represented two cases of thoracic or thoracolumbar OPLL. The first patient was a 72-year-old woman who had a beak-type OPLL at the T11/12. The second was a 45-year-old woman who had a beak-type OPLL at the T12/L1. We performed circumferential spinal cord decompression through a single posterior approach with microendoscopy in both cases. The postoperative computed tomography revealed the complete removal of the OPLL, and the magnetic resonance imaging confirmed adequate decompression of the spinal cord. Preoperative symptoms were substantially improved in both patients. To date, we have used this novel technique to treat five patients with thoracic or thoracolumbar OPLL. This new surgical technique is likely to be useful in patients with a beak-type OPLL of the thoracic or thoracolumbar spine

Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3.

植物由来成分であるプテロシンBはSIK3を阻害し変形性関節症の治療薬開発のリード化合物となる. 京都大学プレスリリース. 2016-03-31.Yahara, Y., Takemori, H., Okada, M. et al. Correction: Corrigendum: Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3. Nat Commun 7, 12117 (2016).Osteoarthritis is a common debilitating joint disorder. Risk factors for osteoarthritis include age, which is associated with thinning of articular cartilage. Here we generate chondrocyte-specific salt-inducible kinase 3 (Sik3) conditional knockout mice that are resistant to osteoarthritis with thickened articular cartilage owing to a larger chondrocyte population. We also identify an edible Pteridium aquilinum compound, pterosin B, as a Sik3 pathway inhibitor. We show that either Sik3 deletion or intraarticular injection of mice with pterosin B inhibits chondrocyte hypertrophy and protects cartilage from osteoarthritis. Collectively, our results suggest Sik3 regulates the homeostasis of articular cartilage and is a target for the treatment of osteoarthritis, with pterosin B as a candidate therapeutic

Incidence of endocrine-related immune-related adverse events in Japanese subjects with various types of cancer

BackgroundImmune checkpoint inhibitors (ICIs), such as cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors, programmed cell death protein 1 (PD-1) inhibitors, and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors, are often used to treat a variety of malignancies. ICIs are known to cause endocrine-related immune-related adverse events (irAEs), but the incidence varies among reports and/or agents. This study evaluated the incidence of endocrine-related irAEs in patients who were treated with ICIs in Japan.MethodThis single-center, retrospective, observational study examined the incidence and clinical characteristics of endocrine-related irAEs in 466 participants who were treated with ICIs at Kawasaki Medical School Hospital.ResultThe mean age of participants with and without endocrine-related irAEs was 69.1 ± 1.8 years and 68.1 ± 1.1 years, respectively, with no difference between them. The overall incidence of any endocrine-related irAEs among the participants was 25.5%. Hypothyroidism was prevalent in 24.3%, hypoadrenocorticism in 3.2%, hypopituitarism in 0.9%, and insulin-dependent diabetes mellitus in 1.1%. Participants receiving combination therapy with CTLA-4 and PD-1 inhibitors had a significantly higher incidence of endocrine-related irAEs than those receiving monotherapy.ConclusionEndocrine-related irAEs correlated significantly with survival and mean observation period. There was substantial difference in the incidence of endocrine-related irAEs among various types of ICIs and types of cancer. We should bear in mind that endocrine testing is necessary during the treatment with ICIs

Establishment of a new human osteosarcoma cell line, UTOS-1: cytogenetic characterization by array comparative genomic hybridization

The cytogenetic characteristics of osteosarcoma (OS) remain controversial. The establishment of a new human OS cell line may improve the characterization. We report the establishment of a new human osteosarcoma cell line, UTOS-1, from a typical osteoblastic OS of an 18-year-old man. Cultured UTOS-1 cells are spindle-shaped, and have been maintained in vitro for over 50 passages in more than 2 years. Xenografted UTOS-1 cells exhibit features typical of OS, such as production of osteoid or immature bone matrix, and proliferation potency in vivo. UTOS-1 also exhibit morphological and immunohistochemical characteristics typical of osteoblastic OS. Chromosomal analysis by G-band show 73~85 chromosomes with complicated translocations. Array CGH show frequent gains at locus DAB2 at chromosome 5q13, CCND2 at 12p13, MDM2 at 12q14.3-q15, FLI and TOP3A at 17p11.2-p12 and OCRL1 at Xq25, and show frequent losses at HTR1B at 6q13, D6S268 at 6q16.3-q21, SHGC17327 at 18ptel, and STK6 at 20q13.2-q13.3. The UTOS-1 cell line may prove useful for biologic and molecular pathogenetic investigations of human OS