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Lipocalin 2: A New Mechanoresponding Gene Regulating Bone Homeostasis.

Rucci, Nadia and Capulli, Mattia and Piperni, Sara Gemini and Cappariello, Alfredo and Lau, Patrick and Frings-Meuthen, Petra and Heer, Martina and Teti, Anna (2014) Lipocalin 2: A New Mechanoresponding Gene Regulating Bone Homeostasis. Journal of Bone and Mineral Research. Wiley. DOI: 10.1002/jbmr.2341 ISSN 0884-0431

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Abstract

Mechanical loading represents a crucial factor in the regulation of skeletal homeostasis. Its reduction causes loss of bone mass, eventually leading to osteoporosis. In a previous global transcriptome analysis performed in mouse calvarial osteoblasts subjected to simulated microgravity, the most up-regulated gene compared to unit gravity condition was Lcn2, encoding the adipokine Lipocalin 2 (LCN2), whose function in bone metabolism is poorly known. To investigate the mechanoresponding properties of LCN2, we evaluated LCN2 levels in sera of healthy volunteers subjected to bed rest, and found a significant time-dependent increase of this adipokine compared to time 0. We then evaluated the in vivo LCN2 regulation in mice subjected to experimentally-induced mechanical unloading by i) tail suspension, ii) muscle paralysis by botulin toxin A (Botox) or iii) genetically-induced muscular dystrophy (MDX mice), and observed that Lcn2 expression was up-regulated in the long bones of all of them, while physical exercise counteracted this increase. Mechanistically, in primary osteoblasts transfected with LCN2-expression-vector (OBs-Lcn2) we observed that Runx2 and its downstream genes Osterix and Alp were transcriptionally down-regulated, and ALP activity was less prominent versus empty-vector transduced osteoblasts (OBs-empty). OBs-Lcn2 also exhibited an increase of the Rankl/Opg ratio and IL-6 mRNA, suggesting that LCN2 could link osteoblast poor differentiation to enhanced osteoclast stimulation. In fact, incubation of purified mouse bone marrow mononuclear cells with conditioned media from OBs-Lcn2 cultures, or their co-culture with OBs-Lcn2, improved osteoclastogenesis compared to OBs-empty, while treatment with LCN2 had no effect. In conclusion, our data indicate that LCN2 is a novel osteoblast mechanoresponding gene and that its regulation could be central to the pathological response of the bone tissue to low mechanical forces.

Item URL in elib:https://elib.dlr.de/90404/
Document Type:Article
Title:Lipocalin 2: A New Mechanoresponding Gene Regulating Bone Homeostasis.
Authors:
AuthorsInstitution or Email of AuthorsAuthors ORCID iD
Rucci, NadiaDepartment of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, ItalyUNSPECIFIED
Capulli, MattiaDepartment of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, ItalyUNSPECIFIED
Piperni, Sara GeminiDepartment of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, ItalyUNSPECIFIED
Cappariello, AlfredoBambino Gesù Children Hospital, “Istituto di Ricovero e Cura a Carattere Scientifico” (IRCCS), Rome, ItalyUNSPECIFIED
Lau, PatrickRadiation Biology Department, German Aerospace Center (DLR), Institute of Aerospace Medicine, Linder Hoehe, 51147 Cologne (Köln), GermanyUNSPECIFIED
Frings-Meuthen, PetraGerman Aerospace Center (DLR), Institute of Aerospace Medicine, Space Physiology, Cologne, GermanyUNSPECIFIED
Heer, MartinaInstitut für Ernährungswissenschaft, Universität Bonn, GermanyUNSPECIFIED
Teti, AnnaDepartment of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, ItalyUNSPECIFIED
Date:12 August 2014
Journal or Publication Title:Journal of Bone and Mineral Research
Refereed publication:Yes
Open Access:Yes
Gold Open Access:No
In SCOPUS:Yes
In ISI Web of Science:Yes
DOI :10.1002/jbmr.2341
Publisher:Wiley
ISSN:0884-0431
Status:Published
Keywords:LCN2; adipokine; mechanical forces; osteoblasts; osteoclasts; unloading
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Integrative Studien (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Space Physiology
Deposited By: Becker, Christine
Deposited On:27 Aug 2014 13:31
Last Modified:06 Sep 2019 15:19

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