Bone Marrow Adipoq-lineage Progenitors: an Emerging Osteoclast Niche Cell Population

The purpose of this review is to summarize and highlight the recent findings of a novel osteoclastic niche centered on the bone marrow Adipoq-lineage progenitors. We will focus on these novel discoveries to help understand the impact of the unique bone marrow Adipoq-lineage cells on osteoclasts, the bone marrow milieu and the skeleton, discuss the similarities and differences between the Adipoq-lineage cells and other bone marrow stromal progenitors, as well as some important questions that draw increasing attention and need to be addressed.

Osteoclasts are the exclusive bone-resorbing cells important for bone homeostasis. Osteoclastogenesis is essentially induced by Macrophage colony-stimulating factor (M-CSF) and Receptor activator of nuclear factor kappa-Β ligand (RANKL), meanwhile regulated by other cytokines. Osteoblasts have been long believed to be the major partners of osteoclasts through secretion of M-CSF and RANKL. However, recent groundbreaking findings challenged this traditional model and identified the bone marrow Adipoq-lineage progenitors, not osteoblasts or mature adipocytes, as the main cell type supporting osteoclastogenesis through producing M-CSF, RANKL and other osteoclastogenic cytokines. Recent evidence suggests that the functional impact of the bone marrow Adipoq-lineage progenitors on macrophage lineage development and osteoclastogenesis is very significant. Future studies are expected to elucidate the lineage specification of this cell population and how signaling pathways and environmental cues shape this unique osteoclastic niche in physiological and pathological conditions.