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a Institute of Histology and Laboratory Analysis and
b Institute of Morphological Sciences, Center of Cytometry, University "Carlo Bo" of Urbino, Urbino, Italy;
c Department of Histology, Embryology, and Applied Biology and
d Stem Cell Research Center, University of Bologna, Bologna, Italy
Key Words. Mesenchymal stem cell • Matrix metalloproteinase • Tissue inhibitor of metalloproteinases • Gene and protein expression • Differentiation • Osteogenesis • Chondrogenesis • Adipogenesis • Neurogenesis • Myogenesis
Correspondence: Ferdinando Mannello, Ph.D., Istituto di Istologia ed Analisi di Laboratorio, Facoltà di SMFN, Università Studi "Carlo Bo," Via E. Zeppi, 61029 Urbino (PU), Italy. Telephone: +39-0722-351479; Fax: 39-0722-322370; e-mail: f.mannello{at}uniurb.it; Web site: http://www.uniurb.it/istoanalab/index.htm
Received on July 24, 2005;
accepted for publication on September 2, 2005.
Matrix metalloproteinases (MMPs), known as matrixins, are Ca- and Zn-dependent endoproteinases involved in a wide variety of developmental and disease-associated processes, proving to be crucial protagonists in many physiological and pathological mechanisms. The ability of MMPs to alter, by limited proteolysis and through the fine control of tissue inhibitors of metalloproteinases, the activity or function of numerous proteins, enzymes, and receptors suggests that they are also involved in various important cellular functions during development. In this review, we focus on the differentiation of mesenchymal stem cells (including those of the myoblastic, osteoblastic, chondroblastic, neural, and apidoblastic lineages) and the possible, if unexpected, biological significance of MMPs in its regulation. The MMP system has been implicated in several differentiation events that suggests that it mediates the proliferative and prodifferentiating effect of the matrixin proteolytic cascade. We summarize these regulatory effects of MMPs on the differentiation of mesenchymal stem cells and hypothesize on the function of MMPs in the stem cell differentiation processes.
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