biostudies-literatureLi ZAmerican Heart AssociationNICHD NIH HHSNIA NIH HHSNIDDK NIH HHSNCI NIH HHSAmerican Diabetes AssociationNational Institutes of HealthNIAMS NIH HHSNIGMS NIH HHSe160915https://www.ebi.ac.uk/biostudies/studies/S-EPMC9675472biostudies-literatureUnknown7(21)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.JCI insightConstitutive bone marrow adipocytes suppress local bone formation.PMC9675472R24 DK092759,DK125513,DK121759,DK130879,R01 AG069795,T32 HD007505,T32 GM007863,R01DK115583,R01AR066028,P30 AR069620,P30 DK020572,P30 DK089503,P30 CA046592P30 DK089503P30 CA046592T32 GM007863P30 AR069620T32 HD00750520-PAF003611-18-PDF-087R24 DK092759P30 DK020572U19 AG060917R01 AG069795R01 DK115583R01 AG066028Bagchi DPMandair GGranger KMacDougald OAYu HAbrishami SHankenson KDLi ZZhu JBowers EMori HSkjaerlund JSinger KHardij JRosen CJfalseConstitutive bone marrow adipocytes suppress local bone formation.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.2022-01-01T00:00:00Z2022 Nov2024-11-06T07:28:00.042Z2024-11-06T07:28:00.042ZS-EPMC96754723604853710.1172/jci.insight.160915