Cressman, A. | bioRxiv Science

bioRxiv2025

Basigin Links Altered Skeletal Stem Cell Lineage Dynamics with Glucocorticoid-induced Bone Loss and Impaired Angiogenesis

Glucocorticoid (GC) induced osteoporosis (GIOP) and osteonecrosis remain a significant health issue with few approved therapies that can treat the bone loss and dysfunction of skeletal vasculature. Therefore, we aimed to investigate the cellular and molecular processes by which GCs affect osteogenesis and angiogenesis, as well as how treatment with parathyroid hormone (hPTH 1-34) modifies these effects in a mouse model of GIOP. GC treatment reduced bone mass through decreased bone formation by skeletal stem cells (SSCs) while also increasing osteoclast mediated resorption. Concomitantly, endothelial cells were increased in numbers but displayed distorted phenotypical features. However, hPTH treatment reversed GC induced changes in osteogenesis and angiogenesis to control levels. Transplantation studies of SSCs combined with molecular analysis by single cell RNA-sequencing and functional testing of primary human cells tied GC-induced skeletal changes to altered stem and progenitor cell differentiation dynamics. This in turn perpetuated reduced osteogenesis and vascular malformation through direct SSC-endothelial crosstalk mediated at least in part by Basigin. Intriguingly, antibody-mediated blockade of Basigin during GC treatment prevented detrimental bone loss. In addition, when administered to aged mice, anti-Basigin therapy reinstated bone remodeling to significantly improve bone mass independent of sex. These findings, while helping to explain the cellular and molecular basis of how hPTH treatment can mitigate GC induced bone loss, provide new therapeutic vantage points for GIOP and other conditions associated with bone loss.

cell biology↗

bioRxiv2022

Impacts and mechanisms of CO2 narcosis in bumble bees: Narcosis depends on dose, caste and mating status and is not induced by anoxia

Carbon dioxide (CO2) is commonly used to immobilize insects and to induce reproduction in bees. However, despite its wide use and potential off-target impacts, its underlying mechanisms are not fully understood. Here we used Bombus impatiens to examine whether CO2 impacts are mediated by anoxia and whether these mechanisms differ between female castes or following mating. We examined the behavior, physiology, and gene expression of workers, mated and virgin queens following exposure to anoxia, hypoxia, full and partial hypercapnia, and control. Hypercapnia and anoxia caused immobilization, but only hypercapnia resulted in behavioral, physiological, and molecular impacts in bees. Recovery from hypercapnia resulted in increased abdominal contractions and took longer in queens. Additionally, hypercapnia activated queens-but inhibited workers ovaries in a dose-dependent manner and caused a depletion of fat-body lipids in both. All responses of hypercapnia were weaker following mating in queens. Analysis of gene expression related to hypoxia and hypercapnia supported the physiological findings in queens, demonstrating that the overall impacts of CO2, excluding virgin queen ovaries, were unique and were not induced by anoxia. This study contributes to our understanding of the impacts and the mechanistic basis of CO2 narcosis in insects and its impacts on bees physiology.

biochemistry↗