Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss

Bone is maintained by coupled activities of bone-forming osteoblasts/osteocytes and bone-resorbing osteoclasts. Alterations in this relationship can lead to pathologic bone loss such as osteoporosis. It well known that osteogenic cells support osteoclastogenesis via production RANKL. Interestingly, our recently identified marrow mesenchymal cell population—marrow adipogenic lineage precursors (MALPs) form a multidimensional network bone—was computationally demonstrated be the most interactive with monocyte-macrophage through high specific expression several osteoclast regulatory factors, including Using an adipocyte-specific Adipoq-Cre label MALPs, we mice RANKL deficiency MALPs have drastic increase trabecular mass long bones vertebrae starting from 1 month age, while their cortical appears normal. This phenotype was accompanied diminished number attenuated formation at surface. Reduced signaling calvarial abolished osteolytic lesions after LPS injections. Furthermore, ovariectomized mice, elevated resorption partially MALPs. In summary, studies critical player controlling remodeling during normal metabolism pathological RANKL-dependent fashion.