Bone Marrow Adipocytes: Key Players in Vascular Niches, Aging, and Disease

Yonggang Fan¹Mai Elkhalek¹Yuheng Zhang¹Lu Liu¹Qi Tian¹Nareekarn Chueakula¹Saravana Ramasamy¹Rinkoo Dalan¹Shukry Habib²Anjali Kusumbe^1*

• ¹Nanyang Technological University, Singapore, Singapore
• ²Universite de Lausanne, Lausanne, Switzerland

Bone marrow adipocytes (BMAs) are emerging as metabolically active endocrine organs within the bone marrow microenvironment, engaging in extensive crosstalk with vascular niches, osteogenic cells, and hematopoietic compartments. In aging and metabolic disorders, mesenchymal and adipocyte progenitors undergo significant quantitative and qualitative transformations that shift from osteogenesis toward adipogenesis. This enhanced adipogenic profile alters the secretion of key adipokines and cytokines, thereby impairing endothelial function, destabilizing the vascular niche, and reducing hematopoietic stem cell supportculminating in bone fragility and disrupted blood cell production. Central to these alterations are pivotal signaling pathways, which orchestrate the interplay between BMAs and their surrounding cells. Furthermore, factors like oxidative stress, chronic inflammation, and endocrine dysregulation modulate BMA behavior and exacerbate their impact on marrow homeostasis. In this comprehensive review, we integrate recent advances that elucidate the molecular and cellular mechanisms underlying BMA function and their complex interactions with vascular niches. We also discuss therapeutic strategies designed to modulate BMAmediated pathways and their downstream effects on aging and a range of diseases.