Selective Runx2-II deficiency leads to low-turnover osteopenia in adult mice

Zhousheng Xiao, Hani A. Awad, Shiguang Liu, Josh Mahlios, Shiqin Zhang, Farshid Guilak, Matthew S. Mayo, Leigh Darryl Quarles

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Runx2 transcribes Runx2-II and Runx2-I isoforms with distinct N-termini. Deletion of both isoforms results in complete arrest of bone development, whereas selective loss of Runx2-II is sufficient to form a grossly intact skeleton with impaired endochondral bone development. To elucidate the role of Runx2-II in osteoblast function in adult mice, we examined heterozygous Runx2-II (Runx2-II+/-) and homozygous Runx2-II (Runx2-II-/-)- deficient mice, which, respectively, lack one or both copies of Runx2-II but intact Runx2-I expression. Compared to wild-type mice, 6-week-old Runx2-II +/- had reduced trabecular bone volume (BV/TV%), cortical thickness (Ct.Th), and bone mineral density (BMD), decreased osteoblastic and osteoclastic markers, lower bone formation rates, impaired osteoblast maturation of BMSCs in vitro, and significant reductions in mechanical properties. Homozygous Runx2-II-/- mice had a more severe reduction in BMD, BV/TV%, and Ct.Th, and greater suppression of osteoblastic and osteoclastic markers than Runx2-II+/- mice. Non-selective Runx2+/- mice, which have an equivalent reduction in Runx2 expression due to the lack one copy of Runx2-I and II, however, had an intermediate reduction in BMD. Thus, selective Runx2-II mutation causes diminished osteoblastic function in an adult mouse leading to low-turnover osteopenia and suggest that Runx2-I and II have distinct functions imparted by their different N-termini.

Original languageEnglish
Pages (from-to)345-356
Number of pages12
JournalDevelopmental Biology
Volume283
Issue number2
DOIs
StatePublished - Jul 15 2005
Externally publishedYes

Keywords

  • Cortical bone
  • Hypertrophic chondrocyte
  • Knockout
  • Mouse
  • Osteoblast
  • Osteoclast
  • Osteopenia
  • Remodeling
  • Runx2-II
  • Trabecular bone

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    Xiao, Z., Awad, H. A., Liu, S., Mahlios, J., Zhang, S., Guilak, F., Mayo, M. S., & Quarles, L. D. (2005). Selective Runx2-II deficiency leads to low-turnover osteopenia in adult mice. Developmental Biology, 283(2), 345-356. https://doi.org/10.1016/j.ydbio.2005.04.028