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  • RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss.

RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss.

EMBO reports (2021-06-15)
Yan Hu, Xiaoqun Li, Xin Zhi, Wei Cong, Biaotong Huang, Huiwen Chen, Yajun Wang, Yinghua Li, Lipeng Wang, Chao Fang, Jiawei Guo, Ying Liu, Jin Cui, Liehu Cao, Weizong Weng, Qirong Zhou, Sicheng Wang, Xiao Chen, Jiacan Su
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.

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