Hao1 Is Not a Pathogenic Factor for Ectopic Ossifications but Functions to Regulate the TCA Cycle In Vivo

Atsushi Kimura, Akiyoshi Hirayama, Tatsuaki Matsumoto, Yuiko Sato, Tami Kobayashi, Satsuki Ikeda, Midori Maruyama, Mari Kaneko, Mayo Shigeta, Eri Ito, Tomoya Soma, Kana Miyamoto, Tomoyoshi Soga, Masaru Tomita, Akihito Oya, Morio Matsumoto, Masaya Nakamura, Arihiko Kanaji, Takeshi Miyamoto

Research output: Contribution to journalArticlepeer-review

Abstract

Ossification of the posterior longitudinal ligament (OPLL), a disease characterized by the ectopic ossification of a spinal ligament, promotes neurological disorders associated with spinal canal stenosis. While blocking ectopic ossification is mandatory to prevent OPLL development and progression, the mechanisms underlying the condition remain unknown. Here we show that expression of hydroxyacid oxidase 1 (Hao1), a gene identified in a previous genome-wide association study (GWAS) as an OPLL-associated candidate gene, specifically and significantly decreased in fibroblasts during osteoblast differentiation. We then newly established Hao1-deficient mice by generating Hao1-flox mice and crossing them with CAG-Cre mice to yield global Hao1-knockout (CAG-Cre/Hao1flox/flox; Hao1 KO) animals. Hao1 KO mice were born normally and exhibited no obvious phenotypes, including growth retardation. Moreover, Hao1 KO mice did not exhibit ectopic ossification or calcification. However, urinary levels of some metabolites of the tricarboxylic acid (TCA) cycle were significantly lower in Hao1 KO compared to control mice based on comprehensive metabolomic analysis. Our data indicate that Hao1 loss does not promote ectopic ossification, but rather that Hao1 functions to regulate the TCA cycle in vivo.

Original languageEnglish
Article number82
JournalMetabolites
Volume12
Issue number1
DOIs
Publication statusPublished - 01-2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology

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