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

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:131

Enthalten in:

The Journal of clinical investigation - 131(2021), 2 vom: 19. Jan.

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Adiponectin
Adipoq protein, mouse
Bone Biology
Bone marrow differentiation
Journal Article
RANK Ligand
Research Support, N.I.H., Extramural
Tnfsf11 protein, mouse

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

doi:

10.1172/JCI140214

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM317738275