Browsing by Subject "Cartilage"

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Fuz Regulates Craniofacial Development through Tissue Specific Responses to Signaling Factors
(Public Library of Science, 2011-09-14) Zhang, Zichao; Wlodarczyk, Bogdan J.; Niederreither, Karen; Venugopalan, Shankar; Florez, Sergio; Finnell, Richard H.; Amendt, Brad A.
The planar cell polarity effector gene Fuz regulates ciliogenesis and Fuz loss of function studies reveal an array of embryonic phenotypes. However, cilia defects can affect many signaling pathways and, in humans, cilia defects underlie several craniofacial anomalies. To address this, we analyzed the craniofacial phenotype and signaling responses of the Fuz−/− mice. We demonstrate a unique role for Fuz in regulating both Hedgehog (Hh) and Wnt/β-catenin signaling during craniofacial development. Fuz expression first appears in the dorsal tissues and later in ventral tissues and craniofacial regions during embryonic development coincident with cilia development. The Fuz−/− mice exhibit severe craniofacial deformities including anophthalmia, agenesis of the tongue and incisors, a hypoplastic mandible, cleft palate, ossification/skeletal defects and hyperplastic malformed Meckel's cartilage. Hh signaling is down-regulated in the Fuz null mice, while canonical Wnt signaling is up-regulated revealing the antagonistic relationship of these two pathways. Meckel's cartilage is expanded in the Fuz−/− mice due to increased cell proliferation associated with the up-regulation of Wnt canonical target genes and decreased non-canonical pathway genes. Interestingly, cilia development was decreased in the mandible mesenchyme of Fuz null mice, suggesting that cilia may antagonize Wnt signaling in this tissue. Furthermore, expression of Fuz decreased expression of Wnt pathway genes as well as a Wnt-dependent reporter. Finally, chromatin IP experiments demonstrate that β-catenin/TCF-binding directly regulates Fuz expression. These data demonstrate a new model for coordination of Hh and Wnt signaling and reveal a Fuz-dependent negative feedback loop controlling Wnt/β-catenin signaling.
Non-invasive optical diagnostics of cartilage
(2002) Youn, Jong-in; Milner, Thomas E.
With progressive use of lasers in medical applications, a recent focus of cartilage research has resulted in many reports on the investigation of the photobiological effects as well as development of non-invasive optical diagnostic techniques. Studies of the physical process underlying laser-induced stress relaxation have shown a number of mechanical, thermal and optical effects following laser reshaping of cartilage that need to be better understood to optimize the reshaping procedure for clinical applications. In the study of pathological degradation of cartilage such as osteoarthritis, understanding the kinetics of swelling and deformational behavior as well as morphological changes that occur in response to applied electric stimulation will be important to delineate the electro- mechanical mechanisms and rate- limiting processes that govern electromechanical behavior. Studies described in my dissertation are directed toward development of optical feedback control techniques for laser-assisted cartilage reshaping, and optical diagnosis for osteoarthritis. Although my work was directed toward these objectives, solution of many associated problems in the course of my work require scientific and engineering developments that may have benefits outside of those demonstrated here. In feedback control for laser assisted cartilage reshaping, preliminary photothermal effect assessment was performed using Fourier transform infrared spectroscopy. Results of this study may be useful for quantitative investigation of the relationship between the clinically important phenomenon of accelerated stress relaxation and kinetics of macromolecular denaturation in cartilage. For feedback control for laser assisted cartilage reshaping, the depth-resolved phase retardation measurements were performed using polarization sensitive optical coherence tomography (PS-OCT). The measurements of phase retardation changes in cartilage accompanying laser irradiation may be useful to better identify the biophysical transformation responsible for stress relaxation in cartilage and develop an optical feedback control procedure. In optical diagnosis for osteoarthritis, electrokinetic surface displacement and optical phase delays depending on applied excitation voltage and frequency were measured in cartilage using differential phase optical coherence tomography (DP-OCT). The electrokinetic measurements with application o f electric voltage to excite deformation show the measured interferometric surface displacement increased with increasing applied voltage and decreased with increasing excitation frequency. In the electrokinetic response of cartilage, measured optical phase delay between the surface displacement response and excitation waveform varies inversely to the excitation frequency. The investigation of electrokinetic behavior using DP-OCT may be used to develop a non-invasive optical technique for providing a sensitive indicator of cartilage viability on the molecular-level and possibly detecting early degradative changes in cartilage associated with osteoarthritis.