The osteocyte transcriptome shows major temporal changes during maturation and sexual dimorphism in adulthood — ASN Events
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The osteocyte transcriptome shows major temporal changes during maturation and sexual dimorphism in adulthood (#125)

Scott E Youlten 1 2 , Alexander P Corr 1 3 , James T Smith 1 3 , Paul A Baldock 1 2 , John A Eisman 1 2 4 , J.H. Duncan Bassett 5 , Graham R Williams 5 , Peter I Croucher 1 2
  1. The Division of Bone Biology, The Garvan Institute of Medical Research, Sydney, NSW, Australia
  2. St Vincent’s Clinical School, Faculty of Medicine, UNSW Australia, Sydney, NSW, Australia
  3. Faculty of Science, University of Bath, Bath, BA2 7AY, United Kingdom
  4. School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, Australia
  5. Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London, W12 0NN, United Kingdom

The skeleton undergoes major structural, functional and sex-specific changes during postnatal development, maturation and aging. Osteocytes are critical regulators of skeletal biology and may orchestrate these changes. However, little is known about the transcriptome of these cells and how it varies with age and differs between sexes. We hypothesised that osteocytes control skeletal development and bone maintenance, through temporal and sex-specific changes in gene expression.

To test this hypothesis, we determined gene expression in primary-osteocytes from the humeri of 4, 10, 16 and 26-week-old male and female mice (n=5, per age/sex) using non-biased whole transcriptome analysis. Differential expression was defined with a false discovery rate of p<0.05, and weighted gene co-expression network analysis (sex) and DAVID analysis (temporal) were performed.

1925 genes were temporally regulated. 94% (1816 genes) changed between 4 and 10 weeks, during deceleration of linear growth. Pathways enriched for differentially expressed genes were associated with bone formation, including Wnt signalling, osteoblast development and ossification.

2149 genes were differentially expressed between sexes. 99% (2133 genes) occurred from 16 weeks onwards. Two clusters of co-expression with significant sex-related patterns were a 215 gene cluster regulating bone resorption (p<5.9x10-9), with greater expression levels in female mice, and a 90 gene cluster of neural genes enriched for processes including neuron differentiation and dendrite morphogenesis (p<4.1x10-7), also increasing in females.

This study defines temporal and sexually dimorphic differences in the osteocyte transcriptome; reflecting early changes in bone formation in both sexes during skeletal development and growth. In contrast, in adulthood and aging, the osteocyte transcriptome differs between males and females consistent with differences in bone resorption. Thus, dynamic and sexually dimorphic changes in the osteocyte transcriptome demonstrate their essential role in skeletal development and maintenance. Elucidation of the pathways that control these processes will be fundamental to our understanding of bone biology.