Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss
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.
Errataetall: |
CommentIn: EMBO Rep. 2021 Jul 5;22(7):e52986. - PMID 34121307 |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:131 |
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Enthalten in: |
The Journal of clinical investigation - 131(2021), 2 vom: 19. Jan. |
Sprache: |
Englisch |
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Beteiligte Personen: |
Yu, Wei [VerfasserIn] |
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Links: |
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Themen: |
Adiponectin |
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Anmerkungen: |
Date Completed 09.09.2021 Date Revised 09.09.2021 published: Print CommentIn: EMBO Rep. 2021 Jul 5;22(7):e52986. - PMID 34121307 Citation Status MEDLINE |
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doi: |
10.1172/JCI140214 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM317738275 |
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245 | 1 | 0 | |a Bone marrow adipogenic lineage precursors promote osteoclastogenesis in bone remodeling and pathologic bone loss |
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520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Bone Biology | |
650 | 4 | |a Bone marrow differentiation | |
650 | 7 | |a Adiponectin |2 NLM | |
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700 | 1 | |a Zhong, Leilei |e verfasserin |4 aut | |
700 | 1 | |a Yao, Lutian |e verfasserin |4 aut | |
700 | 1 | |a Wei, Yulong |e verfasserin |4 aut | |
700 | 1 | |a Gui, Tao |e verfasserin |4 aut | |
700 | 1 | |a Li, Ziqing |e verfasserin |4 aut | |
700 | 1 | |a Kim, Hyunsoo |e verfasserin |4 aut | |
700 | 1 | |a Holdreith, Nicholas |e verfasserin |4 aut | |
700 | 1 | |a Jiang, Xi |e verfasserin |4 aut | |
700 | 1 | |a Tong, Wei |e verfasserin |4 aut | |
700 | 1 | |a Dyment, Nathaniel |e verfasserin |4 aut | |
700 | 1 | |a Liu, X Sherry |e verfasserin |4 aut | |
700 | 1 | |a Yang, Shuying |e verfasserin |4 aut | |
700 | 1 | |a Choi, Yongwon |e verfasserin |4 aut | |
700 | 1 | |a Ahn, Jaimo |e verfasserin |4 aut | |
700 | 1 | |a Qin, Ling |e verfasserin |4 aut | |
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