Osteoclasts activation by receptor activator of NF-κB ligand (RANKL) enhanced the mobilization of hematopoietic progenitor cells from the bone marrow in acute injury (87.10)

Abstract

Osteoclasts (OCLs) are specialized cells responsible for physiological bone resorption and as well as pathologic bone loss. In addition to unique ability to resorb bone, OCLs also play potential role in the mobilization of hematopoietic progenitor cells from bone marrow, particularly under various stress stimuli(e.g. hypoxia, injury or inflammation). We investigated effect of activated OCLs on the stem niche whether lead to mobilization of hematopoietic progenitors under liver specific injury, which was established in our previous acute liver disease study. We exposed mice to stress situation by inducing liver injury with CCl4 or combination of additional injecting of RANKL to activate OCLs, and compared the effect on the mobilization of hematopoietic progenitor cells from the BM. To investigate OCLs involved mechanism underlying mobilization, we induced activated OCLs from RAW 264.7 cell line through stimulation with RANKL and quantified the level of stem cell niche component, SDF-1 on the osteblasts and CXCR4 on the bone marrow cells(BMCs), after culturing with supernatants from activated OCLs. As a result, Under the stress situation in vivo, the mobilized hematopoietic progenitor cells were significantly increased after RANKL treatment under liver specific injury. Moreover, we found that functional OCLs cleaved SDF-1α on the osteoblasts and increased CXCR4 expression on the BMCs in vitro. These results suggest that OCLs might be involved in alteration of the interaction between SDF-1 and CXCR4 leading to mobilization of hematopoietic progenitor cells from the BM.

Breast cancer at bone metastatic sites: recent discoveries and treatment targets

“…Less evident is the role of osteoclasts in the pre-clinical stages of bone metastases. The current paradigm of HSC niche suggests that osteoblasts maintain HSC at bone marrow while osteoclasts favor mobilization of vascular progenitors towards blood stream (Aicher et al 2008;Brouard et al 2010;Cho et al 2010;Kollet et al 2007Kollet et al , 2006. Do osteoclasts help mobilize dormant cancer cells and initiate cancer spread?…”