Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice
Authors:
- Noopur RajeNRNoopur Raje
- Jesse A. SchoonmakerJSJesse A. Schoonmaker
- Julie C. LiuJLJulie C. Liu
- Teru HideshimaTHTeru Hideshima
- Marc N. WeinMWMarc N. Wein
- Dallas C. JonesDJDallas C. Jones
- Sonia ValletSVSonia Vallet
- Mary L. BouxseinMBMary L. Bouxsein
- Samantha PozziSPSamantha Pozzi
- Shweta ChhetriSCShweta Chhetri
- Y. David SeoYSY. David Seo
- 24 January 2008
- journal article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 118 (2) , 491-504
Abstract
Drug targeting of adult stem cells has been proposed as a strategy for regenerative medicine, but very few drugs are known to target stem cell populations in vivo. Mesenchymal stem/progenitor cells (MSCs) are a multipotent population of cells that can differentiate into muscle, bone, fat, and other cell types in context-specific manners. Bortezomib (Bzb) is a clinically available proteasome inhibitor used in the treatment of multiple myeloma. Here, we show that Bzb induces MSCs to preferentially undergo osteoblastic differentiation, in part by modulation of the bone-specifying transcription factor runt-related transcription factor 2 (Runx-2) in mice. Mice implanted with MSCs showed increased ectopic ossicle and bone formation when recipients received low doses of Bzb. Furthermore, this treatment increased bone formation and rescued bone loss in a mouse model of osteoporosis. Thus, we show that a tissue-resident adult stem cell population in vivo can be pharmacologically modified to promote a regenerative function in adult animals.Keywords
This publication has 44 references indexed in Scilit:
- MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclastsBlood, 2007
- Ovariectomy of 12-month-old rats: effects on osteoprogenitor numbers in bone cell populations isolated from femur and on histomorphometric parameters of bone turnover in corresponding tibiaCell and tissue research, 2007
- Osteonecrosis of the Jaw — Do Bisphosphonates Pose a Risk?New England Journal of Medicine, 2006
- Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivoBlood, 2006
- Combined treatment with a β-blocker and intermittent PTH improves bone mass and microarchitecture in ovariectomized miceBone, 2006
- Regulation of Adult Bone Mass by the Zinc Finger Adapter Protein Schnurri-3Science, 2006
- Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statementCytotherapy, 2006
- New insights into the propagation of fatigue damage in cortical bone using confocal microscopy and chelating fluorochromesEuropean Journal of Morphology, 2005
- Isolation of Mouse Marrow Mesenchymal Progenitors by a Novel and Reliable MethodStem Cells, 2003
- Differentiation of Human Marrow Stromal Precursor Cells: Bone Morphogenetic Protein-2 Increases OSF2/CBFA1, Enhances Osteoblast Commitment, and Inhibits Late Adipocyte MaturationJournal of Bone and Mineral Research, 1999