The Matricellular Extracellular Matrix Protein Thrombospondin-2 Affects Pro-lysyl Oxidase Protein Levels in Primary Osteoblast Lineage Cells
Brodsky, Allie J.
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Thrombospondin-2 (TSP2) is a matricellular extracellular matrix (ECM) protein that regulates collagen fibrillogenesis. It is expressed primarily in tissues of musculoskeletal origin. This study examines the levels of pro-lysyl oxidase (pro-LOX) in primary osteoblast lineage cells harvested from wild-type (WT) and TSP2-null mice, as well as measuring the impact of adenoviral rescue of TSP2-null cells. Western blot analysis of pro-LOX in TSP2-null cells showed that pro-LOX levels were elevated in cell-ECM layers of TSP2-null cells. Unexpectedly, pro-LOX levels in cell-conditioned medium were also increased over TSP2-null with adenoviral TSP2 transduction. These data suggest that our previously LOX- dependent mechanism for processing collagen may be more complicated than previously known. However, our rescue studies suggest that TSP2 does not affect pro-LOX expression directly. Determining the interaction between TSP2 and pro-LOX and their influence on the processing of collagen could lead to the discovery of new targets for clinical treatment of osteoporosis and other diseases affecting bone quality.
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