BM adipocytes (BMAd) are a unique cell population derived from BM mesenchymal progenitors and marrow adipogenic lineage precursors. Although they have long been considered to be a space filler within bone cavities, recent studies have revealed important physiological roles in hematopoiesis and bone metabolism. To date, the approaches used to study BMAd function have been confounded by contributions by nonmarrow adipocytes or by BM stromal cells. To address this gap in the field, we have developed a BMAd-specific Cre mouse model to deplete BMAds by expression of diphtheria toxin A (DTA) or by deletion of peroxisome proliferator-activated receptor gamma (Pparg). We found that DTA-induced loss of BMAds results in decreased hematopoietic stem and progenitor cell numbers and increased bone mass in BMAd-enriched locations, including the distal tibiae and caudal vertebrae. Elevated bone mass appears to be secondary to enhanced endosteal bone formation, suggesting a local effect caused by depletion of BMAd. Augmented bone formation with BMAd depletion protects mice from bone loss induced by caloric restriction or ovariectomy, and it facilitates the bone-healing process after fracture. Finally, ablation of Pparg also reduces BMAd numbers and largely recapitulates high–bone mass phenotypes observed with DTA-induced BMAd depletion.
Ziru Li, Devika P. Bagchi, Junxiong Zhu, Emily Bowers, Hui Yu, Julie Hardij, Hiroyuki Mori, Katrina Granger, Jon Skjaerlund, Gurjit Mandair, Simin Abrishami, Kanakadurga Singer, Kurt D. Hankenson, Clifford J. Rosen, Ormond A. MacDougald
Usage data is cumulative from May 2023 through May 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 1,171 | 575 |
238 | 196 | |
Figure | 246 | 6 |
Supplemental data | 90 | 32 |
Citation downloads | 32 | 0 |
Totals | 1,777 | 809 |
Total Views | 2,586 |
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.