Journal article

Tissue Inhibitor of Metalloproteinase-3 (TIMP-3) Regulates Hematopoiesis and Bone Formation In Vivo

Yi Shen, Ingrid G Winkler, Valerie Barbier, Natalie A Sims, Jean Hendy, Jean-Pierre Levesque



BACKGROUND: Tissue inhibitor of metalloproteinases-3 (TIMP-3) inhibits matrix metalloproteinases and membrane-bound sheddases. TIMP-3 is associated with the extracellular matrix and is expressed in highly remodeling tissues. TIMP-3 function in the hematopoietic system is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We now report that TIMP-3 is highly expressed in the endosteal region of the bone marrow (BM), particularly by osteoblasts, endothelial and multipotent mesenchymal stromal cells which are all important cellular components of hematopoietic stem cell (HSC) niches, whereas its expression is very low in mature leukocytes and hematopoietic stem and progenitor cells. A possible role of TIMP..

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Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

This work was supported by project grants (#288701 and #434515 to JPL) and a research fellowship (#488817 to IGW) from the National Health and Medical Research Council of Australia, an Australian Postgraduate Award and Mater Medical Research Institute top-up scholarship (YS), and a senior research fellowship from the Cancer Council of Queensland (JPL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.