Abstract
Chemokine CCL4 (MIP-1β) is released from osteoblast cells to restore the homeostasis of hematopoietic stem cells during the activation of bone marrow. In this study, we investigated the function of CCL4 and its receptor CCR5 during osteoclastogenesis. CCL4 promoted the migration and viability of preosteoclast cells. However, CCL4 had no direct effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in mouse preosteoclast cells. In addition, CCR5 expression was rapidly reduced by RANKL treatment, which was recovered by IFN-γ during osteoclastogenesis. CCR5 downregulation by RANKL was mediated by MEK and JNK in preosteoclast cells and promoted osteoclastogenesis. These results suggest that CCL4 can enhance the recruitment of preosteoclasts to bone in the early stage, and the reduction of CCR5 promotes osteoclastogenesis when RANKL is prevalent.
Highlights
The stem cell niche is a microenvironment where stem cells interact with themselves, other cells, secreted factors, immunological factors, the extracellular matrix, and physical factors[1]
Receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis is not blocked by CCL4 treatment, which is supported by the observation that RANKL-mediated induction of CtsK and MMP9 transcript is not inhibited by CCL4 treatment (Fig. 1c, d)
These results suggested that CCL4 might not play a role in osteoclast differentiation process itself induced by macrophage colony-stimulating factor (M-CSF) and RANKL
Summary
The stem cell niche is a microenvironment where stem cells interact with themselves, other cells, secreted factors, immunological factors, the extracellular matrix, and physical factors[1]. The hematopoietic stem cell niche is important in hematopoiesis, inflammation, and bone homeostasis. Hematopoietic stem cells (HSC) are precursor cells of blood and immune cells, including monocytes/macrophages that arise from osteoclast progenitor cells[2]. There are two forms of hematopoietic stem cell niche: one is an endosteal niche (osteoblastic niche), and the other is a sinusoidal vascular niche. The osteoblastic niche contributes to the maintenance of the HSC balance, quiescence, and activation[3]. Bone marrow is a niche where HSCs are maintained and hematopoiesis and osteoclastogenesis occur. Bone marrow is suppressed by diverse sources of stress conditions, such as oxidation, anemia, hypoxia, radiation, cytotoxic
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
