Neutrophils inhibit bone formation by directly contacting osteoblasts and suppressing osteogenic differentiation

Neutrophils have been extensively studied for their critical roles in supporting immune defense mechanisms, initiating bone regeneration, and promoting angiogenesis. Nonetheless, the influence of neutrophils on physiological conditions, particularly in the context of bone development, remains incompletely understood. In this study, we examined the effects of non-inflammatory neutrophils on bone physiology by depleting Ly6G+ neutrophils and inducing neutropenia through myelosuppression. Our results demonstrated a notable increase in bone mass and a decrease in the bone marrow cavity upon depletion of the neutrophils. These effects were attributed to the direct interaction between neutrophils and osteoblasts, independent of reduced secretion of typical inflammatory cytokines or diminished osteoclast differentiation. This observation suggests a non-inflammatory function of neutrophils within the endosteal microenvironment, where they regulate osteogenic differentiation to preserve optimal bone mass, shape healthy three-dimensional bone trabecular structures, and create ample space for hematopoietic niche development. •Neutrophils have a non-inflammatory role in the bone marrow microenvironment.•Neutrophils are directly involved in inhibiting osteogenic differentiation.•Neutrophils regulate bone mass to provide space for hematopoietic ecological niches.