RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss
- 13 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Reports
- Vol. 22 (7), e52481
- https://doi.org/10.15252/embr.202152481
Abstract
Receptor activator of NF-κB ligand (RANKL) is essential for osteoclast formation and bone remodeling. Nevertheless, the cellular source of RANKL for osteoclastogenesis has not been fully uncovered. Different from peripheral adipose tissue, bone marrow (BM) adipose lineage cells originate from bone marrow mesenchymal stromal cells (BMSCs). Here, we demonstrate that adiponectin promoter-driven Cre expression (AdipoqCre) can target bone marrow adipose lineage cells. We cross the AdipoqCre mice with ranklfl/fl mice to conditionally delete RANKL from BM adipose lineage cells. Conditional deletion of RANKL increases cancellous bone mass of long bones in mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but does not affect cortical bone thickness or resorption of calcified cartilage. AdipoqCre; ranklfl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone (ROS)-induced trabecular bone loss but show bone loss induced by unloading. BM adipose lineage cells therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling under physiological and pathological conditions. Targeting bone marrow adiposity is a promising way of preventing pathological bone loss.Keywords
Funding Information
- National Key Research and Development Program of China (2018YFC2001500)
- Shanghai Municipal Human Resources Development Program for Outstanding Leaders in Medical Disciplines (2017BR011)
- National Natural Science Foundation of China (91749204, 81871099, 81771491)
This publication has 45 references indexed in Scilit:
- RANKL signaling in bone marrow mesenchymal stem cells negatively regulates osteoblastic bone formationBone Research, 2018
- 18β-Glycyrrhetinic Acid Inhibits Osteoclastogenesis In Vivo and In Vitro by Blocking RANKL-Mediated RANK–TRAF6 Interactions and NF-κB and MAPK Signaling PathwaysFrontiers in Pharmacology, 2018
- CCL3 and MMP-9 are induced by TL1A during death receptor 3 (TNFRSF25)-dependent osteoclast function and systemic bone lossBone, 2017
- Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone RegenerationCell Stem Cell, 2017
- Parathyroid Hormone Directs Bone Marrow Mesenchymal Cell FateCell Metabolism, 2017
- Soluble receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin in ankylosing spondylitis: OPG is associated with poor physical mobility and reflects systemic inflammationClinical Rheumatology, 2010
- Effects of risedronate on bone marrow adipocytes in postmenopausal womenOsteoporosis International, 2010
- Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetesDiabetes, Obesity and Metabolism, 2010
- Role of platelet-derived growth factors in physiology and medicineGenes & Development, 2008
- Osteoclast differentiation and activationNature, 2003