Suppression of Osteoarthritis progression by post-natal Induction of Nkx3.2

Biochem Biophys Res Commun. 2021 Sep 24:571:188-194. doi: 10.1016/j.bbrc.2021.07.074. Epub 2021 Jul 27.

Abstract

Osteoarthritis (OA) is an incurable joint disease affecting 240 million elderly population, and major unmet medical needs exist for better therapeutic options for OA. During skeletal development, Nkx3.2 has been shown to promote chondrocyte differentiation and survival, but to suppress cartilage hypertrophy and blood vessel invasion. Here we show that Nkx3.2 plays a key role in osteoarthritis (OA) pathogenesis. Marked reduction of Nkx3.2 expression was observed in three different murine OA models. Consistent with these findings, analyses of surgery-induced and age-driven OA models revealed that cartilage-specific post-natal induction of Nkx3.2 can suppress OA progression in mice. These results suggest that Nkx3.2 may serve as a promising target for OA drug development.

Keywords: Nkx3.2; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Mice
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Osteoarthritis / surgery
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Homeodomain Proteins
  • Nkx3-2 protein, mouse
  • Transcription Factors