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Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice

2008; American Society for Clinical Investigation; Linguagem: Inglês

10.1172/jci33102

1558-8238

Siddhartha Mukherjee, Noopur Raje, Jesse Schoonmaker, Julie C. Liu, Teru Hideshima, Marc N. Wein, Dallas C. Jones, Sonia Vallet, Mary Bouxsein, Samantha Pozzi, Shweta Chhetri, Y. David Seo, Joshua P. Aronson, Chirayu G. Patel, Mariateresa Fulciniti, Louise E. Purton, Laurie H. Glimcher, Jane B. Lian, Gary S. Stein, Kenneth C. Anderson, David T. Scadden,

Bone Metabolism and Diseases

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.