Osteoblast-specific expression of Panx3 is dispensable for postnatal bone remodeling

Bone. 2019 Oct;127:155-163. doi: 10.1016/j.bone.2019.06.008. Epub 2019 Jun 14.

Abstract

Since cost-effective osteoanabolic treatment options remain to be established, it is relevant to identify specific molecules physiologically regulating osteoblast differentiation and/or activity that are principally accessible as drug targets. Specific or predominant gene expression in a given cell type often predicts a relevant function in the respective tissue. Thus, we aimed to identify genes encoding membrane-associated proteins with selective expression in differentiated osteoblasts. We therefore applied an unbiased approach, i.e. Affymetrix Gene Chip hybridization, to compare global gene expression in primary murine osteoblasts at two stages of differentiation. For the most strongly induced genes we analyzed their expression pattern in different tissues, which led us to identify known and unknown osteoblast differentiation markers with predominant expression in bone. One of these genes was Panx3, encoding a transmembrane hemichannel with ill-defined function in skeletal remodeling. To decipher the role of Panx3 in osteoblasts we first generated Panx3-fl/fl mice carrying a Runx2-Cre transgene. Using undecalcified histology followed by bone-specific histomorphometry we did not observe any significant difference between 24 weeks old Cre-negative and Cre-positive littermates. We additionally generated and analyzed mice with ubiquitous Panx3 deletion, where a delay of endochondral ossification did not translate into a detectable skeletal phenotype after weaning, possibly explained by compensatory induction of Panx1. Of note, newborn Panx3-deficient mice displayed significantly reduced serum glucose levels, which was not the case in older animals. Our findings demonstrate that Panx3 expression in osteoblasts is not required for postnatal bone remodeling, which essentially rules out its suitability as a target protein for osteoanabolic medication.

Keywords: Expression analysis; Mouse model; Osteoblast; Panx3.

MeSH terms

  • Animals
  • Animals, Newborn
  • Bone Remodeling*
  • Cell Differentiation / genetics
  • Connexins / deficiency
  • Connexins / metabolism*
  • Gene Expression Regulation
  • Mice, Inbred C57BL
  • Organ Specificity
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Phenotype

Substances

  • Connexins
  • pannexin 3 protein, mouse