Hypoplasia of medial pterygoid process in sphenoid bone relates to decreased mesenchymal cell proliferation in the Runx2-haploinsufficient cleidocranial dysplasia mouse model

Abstract

Objective: Hypoplasia of the medial pterygoid process of the sphenoid bone is a distinct skeletal phenotype in runt-related transcription factor 2 (Runx2) heterozygous mice and patients with cleidocranial dysplasia. The aim of this study was to investigate the involvement of Runx2 in hypoplasia by regulating cell proliferation in the mesenchymal cell condensation region.

Design: A total of thirty mouse embryos were used. The medial pterygoid process region in the Runx2^+/+, Runx2^+/-, and Runx2^-/- mouse embryos were histologically investigated. Immunohistochemistry for Runx2 and proliferating cell nuclear antigen (PCNA) was carried out.

Results: In embryonic day 14.5, mesenchymal cell condensation appeared at the future medial pterygoid process in Runx2^+/+ mice, but was obscure in Runx2^+/- mice. In these areas, cells showed a dual expression of Runx2 and PCNA in both Runx2^+/+ and Runx2^+/- mice. However, the number of Runx2- and PCNA-positive cells was decreased in Runx2^+/- mice. In Runx2^-/- mice, mesenchymal cell condensation appeared on embryonic day 18.5 at the medial pterygoid process region, associated with a few PCNA-positive cells. Moreover, the PCNA-positive cell rate in the medial pterygoid process was significantly lower in Runx2^-/- mice than in Runx2^+/+ and Runx2^+/- mice. On embryonic day 18.5, Runx2^+/- and Runx2^-/- mice showed significantly shorter axial length of medial pterygoid process compared to that in Runx2^+/+ mice.

Conclusions: The present study demonstrates that Runx2 is involved in cell proliferation in the mesenchymal cell condensation region of the medial pterygoid process during mouse embryonic development.

Keywords: Cell proliferation; Mesenchymal cell; Runx2; Secondary cartilage; Sphenoid bone.