Role and Function of Matrix Metalloproteinases in the Differentiation and Biological Characterization of Mesenchymal Stem Cells

Abstract

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. STEM CELLS 2006;24:475-481

Increased release and activity of matrix metalloproteinase‐9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome

“…Even though this is not a proof of a prominent role played by MMP-9 in this process, it must be reminded that there is strong evidence that MMPs play a crucial role during osteogenesis and bone remodelling (32). Their synthesis by osteoblasts has been demonstrated during osteoid degradation prior to resorption of mineralized matrix by osteoclasts, and their activities are regulated by TIMPs (33).…”

Matrix Metalloprotease Activity Is an Essential Link Between Mechanical Stimulus and Mesenchymal Stem Cell Behavior

“…In addition, it is speculated that this protease is involved in the regulation of cell differentiation into the chondrogenic or osteogenic lineage [17]. It has been further hypothesized that additional MMP family members might play a role in MSC differentiation [18]. However, direct evidence remains scarce, and other functional characteristics of MSC biology have not yet been examined with regard to MMP activity.…”

The TGF-β1-Induced Expression of Matrix Metalloproteinases in Mesenchymal Stromal Cells is Influenced by Type of Substrate

“…MMP-3 and MMP-10 were recently detected in endometrial regenerative cells [36], and TGF-β regulates the expression of MMP-3, MMP-10 and MMP-13 in keratinocytes during wound healing [37][38][39]. During chondrogenesis and endochondral ossification, MMP-3 and MMP-13 play an important role in tissue remodelling [25,40,41].…”

“…domain common to all MMPs contains the conserved zinc-binding domain and a unique methionine-turn [22] which play a role in matrix degradation during physiological or pathological processes [22][23][24][25][26]. The stromelysins MMP-3 and MMP-10 degrade a variety of proteins including pro-collagen-I and thus contribute to matrix degradation in bone [27] and cartilage [28].…”