Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss
Year: 2020
Type: article
Abstract: 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 trabecular bone surface. Reduced RANKL signaling in calvarial MALPs abolished osteolytic lesions after LPS injections. Furthermore, in ovariectomized mice, elevated bone resorption was partially attenuated by RANKL deficiency in MALPs. In summary, our studies identified MALPs as a critical player in controlling bone remodeling during normal bone metabolism and pathological bone loss in a RANKL-dependent fashion.
DOI: 10.1172/jci140214
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: University of Pennsylvania, National Institutes of Health, Perelman School of Medicine, University of Pennsylvania, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research, Penn Center for Musculoskeletal Disorders
Awards: Regulation of protein ubiquitination in hematopoietic cytokine signaling, Mechanism of radiotherapy-induced osteoporosis and its treatment, Lnk Regulatory Functions in Hematopoietic Stem Cells, Regulation of skeletal development and homeostasis by IFT protein, Regulation of Ribosome Biogenesis in Hematopoietic Stem Cells, Role of RGS12, a Regulator of G protein Signaling, in Bone Remodeling, Defining the Tendon Lineage to Improve Tissue Engineering Strategies, Dissecting the heterogeneity of bone marrow mesenchymal lineage progenitors, Cell Adhesion Regulation of Osteoclast Maturation, Overall: Resource-based Center for Musculoskeletal Disorders Research (Overall Application)
OpenAlex ID: W3102749211