Adipose tissue

Chemistry

Adipogenesis

Receptor

Gene

Endocrinology

Bone remodeling

Cell biology

Biology

Internal medicine

Pathology

Lineage (genetic)

Bone marrow

Bone remodeling period

Osteoclast

Medicine

Cancer research

Biochemistry

Journal of Clinical Investigation

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 is well known that osteogenic cells support osteoclastogenesis via production of RANKL. Interestingly, our recently identified bone marrow mesenchymal cell population—marrow adipogenic lineage precursors (MALPs) that form a multidimensional cell network in bone—was computationally demonstrated to be the most interactive with monocyte-macrophage lineage cells through high and specific expression of several osteoclast regulatory factors, including RANKL. Using an adipocyte-specific Adipoq-Cre to label MALPs, we demonstrated that mice with RANKL deficiency in MALPs have a drastic increase in trabecular bone mass in long bones and vertebrae starting from 1 month of age, while their cortical bone appears normal. This phenotype was accompanied by diminished osteoclast number and attenuated bone formation at the trab...

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