Contribution of metabolic disease to bone fragility in MAGP1-deficient mice.

Autor: Turecamo SE; Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: sturecamo@wustl.edu., Walji TA; Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: Tezin.Walji@UTSouthwestern.edu., Broekelmann TJ; Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: tbroekel@wustl.edu., Williams JW; Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: jesse.williams@wustl.edu., Ivanov S; INSERM U1065, Mediterranean Center of Molecular Medicine, University of Nice Sophia-Antipolis, Faculty of Medicine, Nice, France. Electronic address: stoyan.ivanov@unice.fr., Wee NK; Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA. Electronic address: wee@uchc.edu., Procknow JD; Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: jdprocknow@gmail.com., McManus MR; Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: mcmanusm@wustl.edu., Randolph GJ; Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: gjrandolph@wustl.edu., Scheller EL; Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, Saint Louis, MO 63110, USA; Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: scheller@wustl.edu., Mecham RP; Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: bmecham@wustl.edu., Craft CS; Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, Saint Louis, MO 63110, USA; Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: clarissa.craft@wustl.edu.
Jazyk: angličtina
Zdroj: Matrix biology : journal of the International Society for Matrix Biology [Matrix Biol] 2018 Apr; Vol. 67, pp. 1-14. Date of Electronic Publication: 2018 Mar 05.
DOI: 10.1016/j.matbio.2018.02.022
Abstrakt: Microfibril-associated glycoprotein-1 (MAGP1) is an extracellular matrix protein that interacts with fibrillin and is involved in regulating the bioavailability of signaling molecules such as TGFβ. Mice with germline MAGP1 deficiency (Mfap2 -/- ) develop increased adiposity, hyperglycemia, insulin resistance, bone marrow adipose tissue expansion, reduced cancellous bone mass, cortical bone thinning and bone fragility. The goal of this study was to assess whether the Mfap2 -/- bone phenotypes were due to loss of MAGP1 locally or secondary to a change in whole body physiology (metabolic dysfunction). To do this, mice with conditional deletion of MAGP1 in the limb skeleton were generated by crossing MAGP1-flox mice (Mfap2 lox/lox ) with Prx1-Cre mice. Mfap2 Prx-/- mice did not show any changes in peripheral adiposity, hyperglycemia or insulin sensitivity, but did have increased bone length and cancellous bone loss that was comparable to the germline Mfap2 -/- knockout. Unlike the germline knockout, marrow adiposity, cortical bone thickness and bone strength in Mfap2 Prx-/- mice were normal. These findings implicate systemic metabolic dysfunction in the development of bone fragility in germline Mfap2 -/- mice. An unexpected finding of this study was the detection of MAGP1 protein in the Mfap2 Prx-/- hematopoietic bone marrow, despite the absence of MAGP1 protein in osseous bone matrix and absent Mfap2 transcript expression at both sites. This suggests MAGP1 from a secondary site may accumulate in the bone marrow, but not be incorporated into the bone matrix, during times of regional MAGP1 depletion.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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