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

S. E. Turecamo, T. A. Walji, T. J. Broekelmann, J. W. Williams, S. Ivanov, N. K. Wee, J. D. Procknow, M. R. McManus, G. J. Randolph, E. L. Scheller, R. P. Mecham, C. S. Craft

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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 (Mfap2lox/lox) with Prx1-Cre mice. Mfap2Prx−/− 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 Mfap2Prx−/− 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 Mfap2Prx−/− 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.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalMatrix Biology
Volume67
DOIs
StatePublished - Apr 2018

Keywords

  • Bone
  • Bone fracture
  • Diabetes
  • Fibrillin
  • MAGP1
  • Marrow adipose tissue
  • Microfibrils
  • Obesity
  • Skeletal fragility

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