Quantifying vocal fold wound-healing biomechanical property changes.

Objectives: Development of novel vocal fold (VF) therapeutics is limited by a lack of standardized, meaningful outcomes. We hypothesize that automated microindentation-based VF biomechanical property mapping matched to histology permits quantitative assessment.

Study Design: Ex vivo.

Bone-Specific Overexpression of PITX1 Induces Senile Osteoporosis in Mice Through Deficient Self-Renewal of Mesenchymal Progenitors and Wnt Pathway Inhibition.

The cellular and molecular mechanisms underlying senile osteoporosis remain poorly understood. In this study, transgenic mCol1α1-Pitx1 mice overexpressing paired-like homeodomain 1 (PITX1), a homeobox transcription factor, rapidly develop a severe type-II osteoporotic phenotype with significant reduction in bone mass and biomechanical strength similar to that seen in humans and reminiscent of the phenotype previously observed in Sca-1 (Ly6a)-null mice. PITX1 plays a critical role in hind limb formation during fetal development, while loss of expression is associated with primary knee/hip osteoarthritis in aging humans.

Automated Indentation Mapping of Vocal Fold Structure and Cover Properties Across Species.

Objectives/hypothesis: Various animal models have been employed to investigate vocal fold (VF) and phonatory function. However, biomechanical testing techniques to characterize vocal fold structural properties vary and have not compared critical properties across species. We adapted a nondestructive, automated indentation mapping technique to simultaneously quantify VF structural properties (VF cover layer and intact VF) in commonly used species based on the hypothesis that VF biomechanical properties are largely preserved across species.

Nuclear accumulation of prohibitin 1 in osteoarthritic chondrocytes down-regulates PITX1 expression.

Objective: To decipher the molecular mechanisms down-regulating PITX1 expression in primary osteoarthritis (OA).

Methods: The functional activity of different PITX1 promoter regions was assessed by luciferase reporter assay. Tandem mass spectrometry coupled to protein sequencing was performed using nuclear extracts prepared from OA chondrocytes, in order to identify proteins bound to DNA regulatory elements.

Skin-derived precursors differentiate into skeletogenic cell types and contribute to bone repair.

Skin-derived precursors (SKPs) are multipotent dermal precursors that share similarities with neural crest stem cells and that can give rise to peripheral neural and some mesodermal cell types, such as adipocytes. Here, we have asked whether rodent or human SKPs can generate other mesenchymally derived cell types, with a particular focus on osteocytes and chondrocytes. In culture, rodent and human foreskin-derived SKPs differentiated into alkaline-positive, collagen type-1-positive, mineralizing osteocytes, and into collagen type-II-positive chondrocytes that secreted chondrocyte-specific proteoglycans.

High-grade glioma formation results from postnatal pten loss or mutant epidermal growth factor receptor expression in a transgenic mouse glioma model.

High-grade gliomas are devastating brain tumors associated with a mean survival of <50 weeks. Two of the most common genetic changes observed in these tumors are overexpression/mutation of the epidermal growth factor receptor (EGFR) vIII and loss of PTEN/MMAC1 expression. To determine whether somatically acquired EGFRvIII expression or Pten loss accelerates high-grade glioma development, we used a previously characterized RasB8 glioma-prone mouse strain, in which these specific genetic changes were focally introduced at 4 weeks of age.

TrkA induces apoptosis of neuroblastoma cells and does so via a p53-dependent mechanism.

Neuroblastoma (NB) is the most frequent solid extracranial tumor in children. Its clinical prognosis correlates with the expression of members of the Trk neurotrophin receptor family, which includes TrkA and TrkB. TrkA expression is associated with favorable prognosis, whereas TrkB expression is associated with poor prognosis.

Induction of caspase-dependent, p53-mediated apoptosis by apigenin in human neuroblastoma.

Neuroblastoma is a pediatric tumor accounting for 15% of childhood cancer deaths and has a poor prognosis in children >1 year of age. We investigated the ability of apigenin, a nonmutagenic dietary flavonoid that has been shown to have antitumor effects in various tumor cell lines, to inhibit growth and induce apoptosis of the human neuroblastoma cell lines NUB-7, LAN-5, and SK-N-BE(2). Apigenin inhibited colony-forming ability and survival, and induced apoptosis of NUB-7 and LAN-5 cells.

Migration of multiple sclerosis lymphocytes through brain endothelium.

Context: T-lymphocyte migration through the blood-brain barrier is a central event in the process of lesion formation in multiple sclerosis (MS).

Objectives: To assess the ability of lymphocytes derived from the peripheral blood of patients with clinically active and inactive MS to migrate across an artificial model of the blood-brain barrier and to elucidate the molecular mechanisms involved in such a process.

Design: We developed an in vitro model of lymphocyte migration using a Boyden chamber coated with a monolayer of human brain microvascular endothelial cells.