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Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss
Wei Yu, … , Jaimo Ahn, Ling Qin
Wei Yu, … , Jaimo Ahn, Ling Qin
Published November 18, 2020
Citation Information: J Clin Invest. 2021;131(2):e140214. https://doi.org/10.1172/JCI140214.
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Research Article Bone biology Article has an altmetric score of 117

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

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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.

Authors

Wei Yu, Leilei Zhong, Lutian Yao, Yulong Wei, Tao Gui, Ziqing Li, Hyunsoo Kim, Nicholas Holdreith, Xi Jiang, Wei Tong, Nathaniel Dyment, X. Sherry Liu, Shuying Yang, Yongwon Choi, Jaimo Ahn, Ling Qin

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Figure 3

MALPs are the major producer of osteoclast regulatory factors in bone.

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MALPs are the major producer of osteoclast regulatory factors in bone.
(...
(A) Ligand-receptor pair analysis of mesenchymal subpopulations with monocytes, macrophages, and osteoclasts. (B) Violin plots of osteoclast regulatory factors in mesenchymal subpopulations. (C) Violin plots of receptors for osteoclast regulatory factors in monocyte-macrophage lineage cells. (D) Representative fluorescence image of TRAP staining in 3-month-old Adipoq/Td/Col1-GFP mouse femur. Scale bar: 500 μm. (E, F) Enlarged images of boxed area in D. Yellow arrows point to Td+ cell processes touching nearby bone surface osteoclasts (white). Note that osteoblasts (green) and osteoclasts are often located at the opposite sides of bone (F). GP, growth plate; CB, cortical bone; BM, bone marrow. Scale bar: 50 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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