Person: Krane, Stephen Martin
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Krane
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Stephen Martin
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Krane, Stephen Martin
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Publication Overview: Destruction of the Extracellular Matrix in Rheumatoid Arthritis(BioMed Central, 2000) Krane, Stephen MartinPublication MMP-13 Regulates Growth of Wound Granulation Tissue and Modulates Gene Expression Signatures Involved in Inflammation, Proteolysis, and Cell Viability(Public Library of Science, 2012) Toriseva, Mervi; Laato, Matti; Carpén, Olli; Ruohonen, Suvi T.; Savontaus, Eriika; Inada, Masaki; Krane, Stephen Martin; Kähäri, Veli-MattiProteinases play a pivotal role in wound healing by regulating cell-matrix interactions and availability of bioactive molecules. The role of matrix metalloproteinase-13 (MMP-13) in granulation tissue growth was studied in subcutaneously implanted viscose cellulose sponge in MMP-13 knockout (Mmp13−/−) and wild type (WT) mice. The tissue samples were harvested at time points day 7, 14 and 21 and subjected to histological analysis and gene expression profiling. Granulation tissue growth was significantly reduced (42%) at day 21 in Mmp13−/− mice. Granulation tissue in Mmp13−/− mice showed delayed organization of myofibroblasts, increased microvascular density at day 14, and virtual absence of large vessels at day 21. Gene expression profiling identified differentially expressed genes in Mmp13−/− mouse granulation tissue involved in biological functions including inflammatory response, angiogenesis, cellular movement, cellular growth and proliferation and proteolysis. Among genes linked to angiogenesis, Adamts4 and Npy were significantly upregulated in early granulation tissue in Mmp13−/− mice, and a set of genes involved in leukocyte motility including Il6 were systematically downregulated at day 14. The expression of Pdgfd was downregulated in Mmp13−/− granulation tissue in all time points. The expression of matrix metalloproteinases Mmp2, Mmp3, Mmp9 was also significantly downregulated in granulation tissue of Mmp13−/− mice compared to WT mice. Mmp13−/− mouse skin fibroblasts displayed altered cell morphology and impaired ability to contract collagen gel and decreased production of MMP-2. These results provide evidence for an important role for MMP-13 in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis.Publication Use of Zoledronic Acid in the Treatment of Paget's Disease(Dove Medical Press, 2007) Seton, Margaret; Krane, Stephen MartinThis review examines the use of zoledronic acid in the treatment of Paget’s disease of bone. It begins with a brief discussion of the theories of pathogenesis of Paget’s disease, its clinical manifestations, and the history of bisphosphonate treatment in this disorder. Risk of oversuppression of bone by the more potent bisphosphonates and their association with avascular necrosis of the jaw are noted.Publication Elucidation of the Potential Roles of Matrix Metalloproteinases in Skeletal Biology(BioMed Central, 2002) Krane, Stephen MartinIrreversible destruction of joint structures is a major feature of osteoarthritis and rheumatoid arthritis. Fibrillar collagens in bone, cartilage and other soft tissues are critical for optimal joint form and function. Several approaches can be used to ascertain the role of collagenases, matrix metalloproteinases, in proteolysis of joint collagens in arthritis. These approaches include identifying spontaneous genetic disorders of the enzymes and substrates in humans and animals, as well as engineering mutations in the genes that encode these proteins in mice. Insights gained from such studies can be used to design new therapies to interrupt these catabolic events.