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.
Siddhartha Mukherjee, Noopur Raje, Jesse A. Schoonmaker, Julie C. Liu, Teru Hideshima, Marc N. Wein, Dallas C. Jones, Sonia Vallet, Mary L. Bouxsein, Samantha Pozzi, Shweta Chhetri, Y. David Seo, Joshua P. Aronson, Chirayu Patel, Mariateresa Fulciniti, Louise E. Purton, Laurie H. Glimcher, Jane B. Lian, Gary Stein, Kenneth C. Anderson, David T. Scadden
Usage data is cumulative from April 2023 through April 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 610 | 83 |
165 | 32 | |
Figure | 153 | 9 |
Supplemental data | 8 | 1 |
Citation downloads | 23 | 0 |
Totals | 959 | 125 |
Total Views | 1,084 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.