Browsing by Author "Fang, Ming"

Now showing 1 - 3 of 3
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    Loss of β-catenin promotes chondrogenic differentiation of aortic valve interstitial cells
    (Ovid Technologies Wolters Kluwer - American Heart Association, 2014-12) Fang, Ming; Alfieri, Christina M.; Hulin, Alexia; Conway, Simon J.; Yutzey, Katherine E.; Department of Pediatrics, IU School of Medicine
    OBJECTIVE: The Wnt/β-catenin signaling pathway has been implicated in human heart valve disease and is required for early heart valve formation in mouse and zebrafish. However, the specific functions of Wnt/β-catenin signaling activity in heart valve maturation and maintenance in adults have not been determined previously. APPROACH AND RESULTS: Here, we show that Wnt/β-catenin signaling inhibits Sox9 nuclear localization and proteoglycan expression in cultured chicken embryo aortic valves. Loss of β-catenin in vivo in mice, using Periostin(Postn)Cre-mediated tissue-restricted loss of β-catenin (Ctnnb1) in valvular interstitial cells, leads to the formation of aberrant chondrogenic nodules and induction of chondrogenic gene expression in adult aortic valves. These nodular cells strongly express nuclear Sox9 and Sox9 downstream chondrogenic extracellular matrix genes, including Aggrecan, Col2a1, and Col10a1. Excessive chondrogenic proteoglycan accumulation and disruption of stratified extracellular matrix maintenance in the aortic valve leaflets are characteristics of myxomatous valve disease. Both in vitro and in vivo data demonstrate that the loss of Wnt/β-catenin signaling leads to increased nuclear expression of Sox9 concomitant with induced expression of chondrogenic extracellular matrix proteins. CONCLUSIONS: β-Catenin limits Sox9 nuclear localization and inhibits chondrogenic differentiation during valve development and in adult aortic valve homeostasis.
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    Nanoscale Structure of Type I Collagen Fibrils: Quantitative Measurement of D-spacing
    (2013-01) Erickson, Blake; Fang, Ming; Wallace, Joseph M.; Orr, Bradford G.; Les, Clifford M.; Banaszak Holl, Mark M.
    This article details a quantitative method to measure the D-periodic spacing of type I collagen fibrils using atomic force microscopy coupled with analysis using a two-dimensional fast fourier transform approach. Instrument calibration, data sampling and data analysis are discussed and comparisons of the data to the complementary methods of electron microscopy and X-ray scattering are made. Examples of the application of this new approach to the analysis of type I collagen morphology in disease models of estrogen depletion and osteogenesis imperfecta (OI) are provided. We demonstrate that it is the D-spacing distribution, not the D-spacing mean, that showed statistically significant differences in estrogen depletion associated with early stage osteoporosis and OI. The ability to quantitatively characterize nanoscale morphological features of type I collagen fibrils will provide important structural information regarding type I collagen in many research areas, including tissue aging and disease, tissue engineering, and gene knockout studies. Furthermore, we also envision potential clinical applications including evaluation of tissue collagen integrity under the impact of diseases or drug treatments.
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    Type I Collagen Exists as a Distribution of Nanoscale Morphologies in Teeth, Bones and Tendons
    (2010-05) Wallace, Joseph M.; Chen, Qishui; Fang, Ming; Erickson, Blake; Orr, Bradford G.; Banaszak Holl, Mark M.
    This study demonstrates that collagen, the most abundant protein in animals, exists as a distribution of nanoscale morphologies in teeth, bones, and tendons. This fundamental characteristic of Type I collagen has not previously been reported and provides a new understanding of the nanoscale architecture of this ubiquitous and important biological nanomaterial. Dentin, bone, and tendon tissue samples were chosen for their differences in cellular origin and function, as well as to compare mineralized tissues with a tissue that lacks mineral in a normal physiological setting. A distribution of morphologies was present in all three tissues, confirming that this characteristic is fundamental to Type I collagen regardless of the presence of mineral, cellular origin of the collagen (osteoblast versus odontoblast versus fibroblast), anatomical location, or mechanical function of the tissue.