Thrombospondin 2, a matricellular protein with diverse functions

Thrombospondin (TSP) 2 is a close relative of TSP1 but differs in its tempo ral and spatial distribution in the mouse. This difference in expression un doubtedly reflects the marked disparity in the DNA sequences of the promote rs in the genes encoding the two proteins. The synthesis of TSP2 occurs pri marily in connective tissues of the developing and growing mouse. In the ad ult animal the protein is again produced in response to tissue injury and i n association with the growth of tumors. Despite the abnormalities in colla gen fibrillogenesis, fragility of skin, and laxity of tendons and ligaments observed in the TSP2-null mouse, TSP2 does not appear to contribute direct ly to the structural integrity of connective tissue elements. Instead, emer ging evidence supports a mode of action of TSP2 'at a distance', i.e. by mo dulating the activity and bioavailability of proteases and growth factors i n the pericellular environment and, very likely, by interaction with cell-s urface receptors. Thus, TSP2 qualifies as a matricellular protein, as defin ed in the introduction to this-minireview series. The phenotype of TSP2-nul l mice has been very helpful in providing clues to the functions of TSP2. I n addition to histological and functional abnormalities in connective tissu es, these mice display an increased vascularity of the dermis and subdermal tissues, increased endosteal bone growth, a bleeding defect, and a marked adhesive defect of dermal fibroblasts. Our laboratory has established that TSP2 binds matrix metalloproteinase 2 (MMP2) and that the adhesive defect i n TSP2-null fibroblasts results from increased MMP2 activity. The investiga tion of the basis for the other defects in the TSP2-null mouse is likely to yield equally interesting results. (C) 2000 Elsevier Science B.V./Internat ional Society of Matrix Biology. All rights reserved.