PMID- 35058428
OWN - NLM
STAT- MEDLINE
DCOM- 20220215
LR  - 20240226
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 13
IP  - 1
DP  - 2022 Jan 20
TI  - Macrophages in epididymal adipose tissue secrete osteopontin to regulate bone 
      homeostasis.
PG  - 427
LID - 10.1038/s41467-021-27683-w [doi]
LID - 427
AB  - Epididymal white adipose tissue (eWAT) secretes an array of cytokines to regulate 
      the metabolism of organs and tissues in high-fat diet (HFD)-induced obesity, but 
      its effects on bone metabolism are not well understood. Here, we report that 
      macrophages in eWAT are a main source of osteopontin, which selectively 
      circulates to the bone marrow and promotes the degradation of the bone matrix by 
      activating osteoclasts, as well as modulating bone marrow-derived macrophages 
      (BMDMs) to engulf the lipid droplets released from adipocytes in the bone marrow 
      of mice. However, the lactate accumulation induced by osteopontin regulation 
      blocks both lipolysis and osteoclastogenesis in BMDMs by limiting the energy 
      regeneration by ATP6V0d2 in lysosomes. Both surgical removal of eWAT and local 
      injection of either clodronate liposomes (for depleting macrophages) or 
      osteopontin-neutralizing antibody show comparable amelioration of HFD-induced 
      bone loss in mice. These results provide an avenue for developing therapeutic 
      strategies to mitigate obesity-related bone disorders.
CI  - (c) 2022. The Author(s).
FAU - Dai, Bingyang
AU  - Dai B
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Xu, Jiankun
AU  - Xu J
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Li, Xu
AU  - Li X
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Huang, Le
AU  - Huang L
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Hopkins, Chelsea
AU  - Hopkins C
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Wang, Honglian
AU  - Wang H
AD  - Research Center for Integrated Medicine, Affiliated Traditional Medicine Hospital 
      of Southwest Medical University, 646000, Luzhou, Sichuan, China.
FAU - Yao, Hao
AU  - Yao H
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Mi, Jie
AU  - Mi J
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Zheng, Lizhen
AU  - Zheng L
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Wang, Jiali
AU  - Wang J
AD  - School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, 
      China.
FAU - Tong, Wenxue
AU  - Tong W
AUID- ORCID: 0000-0003-3462-2740
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Chow, Dick Ho-Kiu
AU  - Chow DH
AUID- ORCID: 0000-0002-2836-3255
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Li, Ye
AU  - Li Y
AUID- ORCID: 0000-0002-2481-6894
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - He, Xuan
AU  - He X
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Hu, Peijie
AU  - Hu P
AD  - Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hung 
      Hom, Hong Kong, China.
FAU - Chen, Ziyi
AU  - Chen Z
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Zu, Haiyue
AU  - Zu H
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China.
FAU - Li, Yixuan
AU  - Li Y
AD  - State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports 
      Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The 
      Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 
      China.
FAU - Yao, Yao
AU  - Yao Y
AD  - State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports 
      Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The 
      Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 
      China.
FAU - Jiang, Qing
AU  - Jiang Q
AD  - State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports 
      Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The 
      Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 
      China.
FAU - Qin, Ling
AU  - Qin L
AUID- ORCID: 0000-0001-6173-6167
AD  - Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology 
      and Innovative Orthopaedic Biomaterial & Drug Translational Research Laboratory, 
      Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, 
      Hong Kong, China. lingqin@cuhk.edu.hk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220120
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (CD11b Antigen)
RN  - 0 (Protein Subunits)
RN  - 106441-73-0 (Osteopontin)
RN  - EC 3.6.1.- (Atp6v0d2 protein, mouse)
RN  - EC 3.6.1.- (Vacuolar Proton-Translocating ATPases)
SB  - IM
MH  - Adipose Tissue/diagnostic imaging/*metabolism
MH  - Adipose Tissue, White/diagnostic imaging/metabolism
MH  - Animals
MH  - Body Weight
MH  - Bone Resorption/pathology
MH  - Bone and Bones/diagnostic imaging/*metabolism
MH  - CD11b Antigen/metabolism
MH  - Cancellous Bone/diagnostic imaging/metabolism
MH  - Diet, High-Fat
MH  - Epididymis/*metabolism
MH  - *Homeostasis
MH  - Inflammation/pathology
MH  - Lipid Metabolism
MH  - Lysosomes/metabolism
MH  - Macrophages/*metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Models, Biological
MH  - Organ Size
MH  - Osteopontin/*metabolism
MH  - Protein Subunits/metabolism
MH  - Vacuolar Proton-Translocating ATPases/metabolism
MH  - X-Ray Microtomography
MH  - Mice
PMC - PMC8776868
COIS- The authors declare no competing interests.
EDAT- 2022/01/22 06:00
MHDA- 2022/02/16 06:00
PMCR- 2022/01/20
CRDT- 2022/01/21 06:05
PHST- 2020/08/15 00:00 [received]
PHST- 2021/11/04 00:00 [accepted]
PHST- 2022/01/21 06:05 [entrez]
PHST- 2022/01/22 06:00 [pubmed]
PHST- 2022/02/16 06:00 [medline]
PHST- 2022/01/20 00:00 [pmc-release]
AID - 10.1038/s41467-021-27683-w [pii]
AID - 27683 [pii]
AID - 10.1038/s41467-021-27683-w [doi]
PST - epublish
SO  - Nat Commun. 2022 Jan 20;13(1):427. doi: 10.1038/s41467-021-27683-w.