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RANKL+ pre-adipocytes stimulate osteoclastogenesis in aging bone marrow
DOI:10.1038/bonekey.2015.22
Holt et al. cultured mesenchymal stem cell-derived cells with a medullary adipocyte lineage in vitro, demonstrating that these cells express RANKL and are able to support the formation of osteoclast-like cells when co-cultured with peripheral blood mononuclear cells. The cells also expressed osteoprotegerin (OPG) and macrophage colony-stimulating factor (M-CSF) at key points in their development.
The results strongly suggest an in vivo link between proliferation of adipocyte precursors and the formation of osteoclasts in the aging bone marrow. This, in turn, leads to bone degradation and osteoporosis.
Takeshita et al. also demonstrated that adipocyte precursors from bone marrow show significantly increased expression of RANKL with an associated down-regulation of OPG. When they used flow-cytometry to analyze bone marrow cells taken from elderly mice, they discovered that all cells expressing Pref-1, the pre-adipocyte marker, were RANKL+. These cells influenced macrophages within the bone marrow to differentiate into osteoclasts.
Editor’s comment: These two papers relating bone marrow pre-adipocytes to the production of the RANK Ligand provide novel insights into the mechanisms by which bone marrow adiposity in the aging may contribute to bone loss. In this sense, the authors redefine what is the chicken (the pre-adipocyte) and what is the egg (the osteoclast) in this catabolic process.
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