Excessive dynamic airway collapse during general anesthesia: a case report.

Background: Excessive dynamic airway collapse (EDAC) is an uncommon cause of high airway pressure during mechanical ventilation. However, EDAC is not widely recognized by anesthesiologists, and therefore, it is often misdiagnosed as asthma.

Case Presentation: A 70-year-old woman with a history of asthma received anesthesia with sevoflurane for a laparotomic cholecystectomy.

BMPRIA is required for osteogenic differentiation and RANKL expression in adult bone marrow mesenchymal stromal cells.

Bone morphogenetic proteins (BMPs) activate the canonical Smad1/5/8 and non-canonical Tak1-MAPK pathways via BMP receptors I and II to regulate skeletal development and bone remodeling. Specific ablation of Bmpr1a in immature osteoblasts, osteoblasts, or osteocytes results in an increase in cancellous bone mass, yet opposite results have been reported regarding the underlying mechanisms. Moreover, the role for BMPRIA-mediated signaling in bone marrow mesenchymal stromal cells (BM-MSCs) has not been explored.

Fibroblast growth factor and canonical WNT/β-catenin signaling cooperate in suppression of chondrocyte differentiation in experimental models of FGFR signaling in cartilage.

Aberrant fibroblast growth factor (FGF) signaling disturbs chondrocyte differentiation in skeletal dysplasia, but the mechanisms underlying this process remain unclear. Recently, FGF was found to activate canonical WNT/β-catenin pathway in chondrocytes via Erk MAP kinase-mediated phosphorylation of WNT co-receptor Lrp6. Here, we explore the cellular consequences of such a signaling interaction.

ERK1 and ERK2 regulate chondrocyte terminal differentiation during endochondral bone formation.

Chondrocytes in the epiphyseal cartilage undergo terminal differentiation prior to their removal through apoptosis. To examine the role of ERK1 and ERK2 in chondrocyte terminal differentiation, we generated Osterix (Osx)-Cre; ERK1(-/-) ; ERK2(flox/flox) mice (conditional knockout Osx [cKOosx]), in which ERK1 and ERK2 were deleted in hypertrophic chondrocytes. These cKOosx mice were grossly normal in size at birth, but by 3 weeks of age exhibited shorter long bones.

Loss of jab1 in osteochondral progenitor cells severely impairs embryonic limb development in mice.

The transcriptional cofactor Jab1 controls cell proliferation, apoptosis, and differentiation in diverse developmental processes by regulating the activity of various transcription factors. To determine the role of Jab1 during early limb development, we developed a novel Jab1(flox/flox) ; Prx1-Cre conditional Knockout (cKO) mutant mouse model in which Jab1 was deleted in the osteochondral progenitor cells of the limb buds. Jab1 cKO mutant mice displayed drastically shortened limbs at birth.

Prx1 and 3.2kb Col1a1 promoters target distinct bone cell populations in transgenic mice.

Bones consist of a number of cell types including osteoblasts and their precursor cells at various stages of differentiation. To analyze cellular organization within the bone, we generated Col1a1CreER-DsRed transgenic mice that express, in osteoblasts, CreER and DsRed under the control of a mouse 3.2kb Col1a1 promoter.

Protective effects of C-type natriuretic peptide on linear growth and articular cartilage integrity in a mouse model of inflammatory arthritis.

Objective: The C-type natriuretic peptide (CNP) signaling pathway is a major contributor to postnatal skeletal growth in humans. This study was undertaken to investigate whether CNP signaling could prevent growth delay and cartilage damage in an animal model of inflammatory arthritis.

Methods: We generated transgenic mice that overexpress CNP (B6.

Protein kinase inhibitor γ reciprocally regulates osteoblast and adipocyte differentiation by downregulating leukemia inhibitory factor.

The protein kinase inhibitor (Pki) gene family inactivates nuclear protein kinase A (PKA) and terminates PKA-induced gene expression. We previously showed that Pkig is the primary family member expressed in osteoblasts and that Pkig knockdown increases the effects of parathyroid hormone and isoproterenol on PKA activation, gene expression, and inhibition of apoptosis. Here, we determined whether endogenous levels of Pkig regulate osteoblast differentiation.

Allying with armored snails: the complete genome of gammaproteobacterial endosymbiont.

Deep-sea vents harbor dense populations of various animals that have their specific symbiotic bacteria. Scaly-foot gastropods, which are snails with mineralized scales covering the sides of its foot, have a gammaproteobacterial endosymbiont in their enlarged esophageal glands and diverse epibionts on the surface of their scales. In this study, we report the complete genome sequencing of gammaproteobacterial endosymbiont.

Ossified choroid plexus papilloma of the fourth ventricle: elucidation of the mechanism of osteogenesis in benign brain tumors.

True ossification within benign brain tumors is rare, and the molecular mechanism for this process is poorly understood. The authors report a case of ossified choroid plexus papilloma (CPP) and analyze it to help elucidate the underlying molecular basis of osteogenesis in benign brain tumors. A 21-year-old man presented with headache and depression that progressed over years.

FGF and ERK signaling coordinately regulate mineralization-related genes and play essential roles in osteocyte differentiation.

To examine the roles of FGF and ERK MAPK signaling in osteocyte differentiation and function, we performed microarray analyses using the osteocyte cell line MLO-Y4. This experiment identified a number of mineralization-related genes that were regulated by FGF2 in an ERK MAPK-dependent manner. Real-time PCR analysis indicated that FGF2 upregulates Ank, Enpp1, Mgp, Slc20a1, and Dmp1 in MLO-Y4 cells.

Genetic inactivation of ERK1 and ERK2 in chondrocytes promotes bone growth and enlarges the spinal canal.

Activating mutations in FGFR3 cause the most common forms of human dwarfism: achondroplasia and thanatophoric dysplasia. In mouse models of achondroplasia, recent studies have implicated the ERK MAPK pathway, a pathway activated by FGFR3, in creating reduced bone growth. Our recent studies have indicated that increased Fgfr3 and ERK MAPK signaling in chondrocytes also causes premature synchondrosis closure in the cranial base and vertebrae, accounting for the sometimes fatal stenosis of the foramen magnum and spinal canal in achondroplasia.

NF449 is a novel inhibitor of fibroblast growth factor receptor 3 (FGFR3) signaling active in chondrocytes and multiple myeloma cells.

The FGFR3 receptor tyrosine kinase represents an attractive target for therapy due to its role in several human disorders, including skeletal dysplasias, multiple myeloma, and cervical and bladder carcinomas. By using molecular library screening, we identified a compound named NF449 with inhibitory activity toward FGFR3 signaling. In cultured chondrocytes and murine limb organ culture, NF449 rescued FGFR3-mediated extracellular matrix loss and growth inhibition, which represent two major cellular phenotypes of aberrant FGFR3 signaling in cartilage.

Extracellular signal-regulated kinase 1 (ERK1) and ERK2 play essential roles in osteoblast differentiation and in supporting osteoclastogenesis.

Osteoblasts and chondrocytes arise from common osteo-chondroprogenitor cells. We show here that inactivation of ERK1 and ERK2 in osteo-chondroprogenitor cells causes a block in osteoblast differentiation and leads to ectopic chondrogenic differentiation in the bone-forming region in the perichondrium. Furthermore, increased mitogen-activated protein kinase signaling in mesenchymal cells enhances osteoblast differentiation and inhibits chondrocyte differentiation.

Mice expressing GFP and CreER in osteochondro progenitor cells in the periosteum.

We generated Prx1CreER-GFP transgenic mice that express tamoxifen-inducible Cre recombinase and GFP under the control of a 2.4 kb Prx1 promoter. The transgene is expressed in osteochondro progenitor cells in the developing limb buds and in a subpopulation of periosteal cells that is closely associated with the cortical bone.

FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway.

Activating mutations in FGFR3 cause achondroplasia and thanatophoric dysplasia, the most common human skeletal dysplasias. In these disorders, spinal canal and foramen magnum stenosis can cause serious neurologic complications. Here, we provide evidence that FGFR3 and MAPK signaling in chondrocytes promote synchondrosis closure and fusion of ossification centers.

Aspects of achondroplasia in the skulls of dwarf transgenic mice: a cephalometric study.

Achondroplasia, the most common short-limbed dwarfism in humans, results from a single nucleotide substitution in the gene for fibroblast growth factor receptor 3 (FGFR3). FGFR3 regulates bone growth in part via the mitogen-activated protein kinase pathway (MAPK). To examine the role of this pathway in chondrocyte differentiation, a transgenic mouse was generated that expresses a constitutively active mutant of MEK1 in chondrocytes and exhibits dwarfing characteristics typical of human achondroplasia, i.

Constitutive activation of MKK6 in chondrocytes of transgenic mice inhibits proliferation and delays endochondral bone formation.

Accumulating in vitro evidence suggests that the p38 mitogen-activated protein kinase (MAPK) pathway is involved in endochondral ossification. To investigate the role of this pathway in endochondral ossification, we generated transgenic mice with expression in chondrocytes of a constitutively active mutant of MKK6, a MAPK kinase that specifically activates p38. These mice had a dwarf phenotype characterized by reduced chondrocyte proliferation, inhibition of hypertrophic chondrocyte differentiation, and a delay in the formation of primary and secondary ossification centers.

Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype.

We generated transgenic mice that express a constitutively active mutant of MEK1 in chondrocytes. These mice showed a dwarf phenotype similar to achondroplasia, the most common human dwarfism, caused by activating mutations in FGFR3. These mice displayed incomplete hypertrophy of chondrocytes in the growth plates and a general delay in endochondral ossification, whereas chondrocyte proliferation was unaffected.