Article
TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation.
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Nature medicine (impact factor:
27.14).
08/2009;
15(7):757-65.
DOI:10.1038/nm.1979
pp.757-65
Source: PubMed
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Article: Ionizing radiation alters myofilament calcium sensitivity in vascular smooth muscle: potential role of protein kinase C.
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ABSTRACT: Radiation exposure increases vascular responsiveness, and this change involves endothelial damage, as well as direct effects on vascular smooth muscle. In this study, we tested the hypothesis that myofilament Ca(2+) sensitivity in vascular smooth muscle is increased from single whole body gamma irradiation (6 Gy). We measured contractile responses from intact and permeabilized rat thoracic aortic rings combined with cytosolic Ca(2+) ([Ca(2+)](i)) measurements. The sensitivity to KCl and phenylephrine increased significantly in tissues from animals on the 9th and 30th days postirradiation compared with control. Irradiation also significantly increased Ca(2+) sensitivity in beta-escin permeabilized smooth muscle on the 9th and 30th days postirradiation. Inhibitors of protein kinase C, chelerythrine, and staurosporine, had no effect on the pCa-tension curves in control permeabilized tissues but significantly decreased Ca(2+) sensitivity in permeabilized tissues on the 9th and 30th days postirradiation. Phorbol dibutyrate (PDBu, 10(-7) M) increased Ca(2+) sensitivity in control skinned smooth muscle but was without effect in irradiated vascular rings. Simultaneous measurement of contractile force and [Ca(2+)](i) showed that myofilament Ca(2+) sensitivity defined as the ratio of force change to [Ca(2+)](i) significantly increased following gamma-irradiation. PDBu (10(-6) M) stimulation of intact aorta produced a sustained contraction, while the increase in [Ca(2+)](i) was transient. In irradiated tissues, PDBu-induced contractions were greater than those seen in control tissues but there was no elevation in [Ca(2+)](i). Taken together, these data strongly support the hypothesis that irradiation increases the sensitivity of vascular smooth muscle myofilaments to Ca(2+) and this effect is dependent on activation of protein kinase C.AJP Regulatory Integrative and Comparative Physiology 10/2005; 289(3):R755-62. · 3.34 Impact Factor -
Article: Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice.
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ABSTRACT: Patients with ulcerative colitis are at risk for colon cancer and frequently have microsatellite instability,which, in turn, is usually associated with inactivation of transforming growth factor (TGF) beta signaling. TGF-beta1 deficiency in mice can lead to colon cancer that is preceded by precancerous lesions having submucosal inflammation and hyperplastic crypts. Germ-free TGF-beta1-deficient mice are free of inflammation, hyperplasia, and cancer, but when reintroduced into a Helicobacter hepaticus-containing specific pathogen-free room, these lesions reappear. Because adenoma/carcinoma but not inflammation/hyperplasia is dependent on the genetic backgrounds tested, colitis is required, but not sufficient, for carcinogenesis. This animal model should provide insight into the protective role of TGF-beta1 in early stages of ulcerative colitis-associated human colon cancer.Cancer Research 12/2002; 62(22):6362-6. · 7.86 Impact Factor -
Article: Skeletal remodeling in health and disease.
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ABSTRACT: The use of genetically manipulated mouse models, gene and protein discovery and the cataloguing of genetic mutations have each allowed us to obtain new insights into skeletal morphogenesis and remodeling. These techniques have made it possible to identify molecules that are obligatory for specific cellular functions, and to exploit these molecules for therapeutic purposes. New insights into the pathophysiology of diseases have also enabled us to understand molecular defects in a way that was not possible a decade ago. This review summarizes our current understanding of the carefully orchestrated cross-talk between cells of the bone marrow and between bone cells and the brain through which bone is constantly remodeled during adult life. It also highlights molecular aberrations that cause bone cells to become dysfunctional, as well as therapeutic options and opportunities to counteract skeletal loss.Nature Medicine 08/2007; 13(7):791-801. · 22.46 Impact Factor
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Keywords
active TGF-beta1
Analyzing mice
bone formation
bone marrow
bone marrow stromal cells
bone mesenchymal
bone resorptive sites
CED-derived mutant TGFB1
couple bone resorption
effective treatment
encoding TGF-beta1
precise coordination
skeletal diseases
SMAD signaling pathway
subsequent bone formation
TGF-beta type
TGF-beta1 activity
TGF-beta1 functions
typical progressive diaphyseal dysplasia
uncoupled bone
