BoneKEy Reports | BoneKEy Watch
Osteoclasts not always needed for HSC production
DOI:10.1038/bonekey.2012.15
Osteopetrosis due to dysfunctional or absent osteoclasts leads to shrinking of the hematopoietic stem cell (HSC) niche cavities in the bone marrow. This is accompanied by compensatory haematopoiesis in the spleen. Osteopetrosis also increases the risk of osteomyelitis, which raises questions about possible myeloid cell lineage and/or functional defects. Researchers in this study used three established models of osteopetrosis (op/op, c-Fos-deficient and RANKL-deficient mice) to clarify the role of osteoclasts in HSC production.
Osteoclasts, and the bone marrow niche cavities they form, are absent in these mice but mobilisation of HSCs and progenitor cells was similar or higher after G-CSF injection compared to wild type mice.
The suggestion that osteoclasts are not always required for HSC production was further borne out by the observation that osteoprotegerin-deficient mice showed reduced HSC and progenitor cell mobilisation after G-CSF injection, despite having higher numbers of osteoclasts. Op/op mice that had their spleens removed were also able to mobilise HSC and progenitor cells as normal. Taken together, these findings may mean that stem cell production can take place in the bone marrow without the activity of osteoclasts, and that osteoclasts may actually be inhibitors of the process.
Editor's comment: G-CSF-induced mobilisation of HSCs is not impaired in osteopetrotic mice, including those that are RANKL-deficient, and is actually increased by alendronate and RANKL antagonists. These key results provide some reassurance regarding the safety of anti-resorptive drugs.
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