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.
Bibliographical noteFunding Information:
The authors declare no conflicts of interest. This work was supported by National Institutes of Health grants HL-053325 and HL-105314 to RPM, and K99-DE024178 and R00-DE024178 to ELS, the American Diabetes Association grant 7-13-JF-16 to CSC, and awards from the Washington University Nutrition and Obesity Research Center and Washington University Musculoskeletal Research Center to CSC. Technical support was provided by Washington University's Nutrition and Obesity Research Center (grant P30-DK-056341), Diabetes Research Center (P30 DK020579), and Musculoskeletal Research Center (P30-AR-057235).
- Bone fracture
- Marrow adipose tissue
- Skeletal fragility
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't