Osteoblast function and bone histomorphometry in a murine model of Rett syndrome

Mary E. Blue, Adele L. Boskey, Stephen B. Doty, Neal S. Fedarko, Mir Ahamed Hossain, Jay R. Shapiro

Research output: Contribution to journalArticlepeer-review

Abstract

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder due to mutations affecting the neural transcription factor MeCP2. Approximately 50% of affected females have decreased bone mass. We studied osteoblast function using a murine model of RTT. Female heterozygote (HET) and male Mecp2-null mice were compared to wild type (WT) mice. Micro-CT of tibia from 5. week-old Mecp2-null mice showed significant alterations in trabecular bone including reductions in bone volume fraction (-. 29%), number (-. 19%), thickness (-. 9%) and connectivity density (-. 32%), and increases in trabecular separation (+. 28%) compared to WT. We also found significant reductions in cortical bone thickness (-. 18%) and in polar moment of inertia (-. 45%). In contrast, cortical and trabecular bone from 8. week-old WT and HET female mice were not significantly different. However, mineral apposition rate, mineralizing surface and bone formation rate/bone surface were each decreased in HET and Mecp2-null mice compared to WT mice. Histomorphometric analysis of femurs showed decreased numbers of osteoblasts but similar numbers of osteoclasts compared to WT, altered osteoblast morphology and decreased tissue synthesis of alkaline phosphatase in Mecp2-null and HET mice. Osteoblasts cultured from Mecp2-null mice, which unlike WT osteoblasts did not express MeCP2, had increased growth rates, but reductions in mRNA expression of type I collagen, Runx2 and Osterix compared to WT osteoblasts. These results indicate that MeCP2 deficiency leads to altered bone growth. Osteoblast dysfunction was more marked in Mecp2-null male than in HET female mice, suggesting that expression of MeCP2 plays a critical role in bone development.

Original languageEnglish (US)
Pages (from-to)23-30
Number of pages8
JournalBone
Volume76
DOIs
StatePublished - Jul 1 2015

Keywords

  • Bone histology
  • MeCP2
  • Micro-CT
  • Osteoblast
  • Osteoclast
  • Rett syndrome

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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