Peroxiredoxin 5 regulates osteogenic differentiation through interaction with hnRNPK during bone regeneration

Elife. 2023 Feb 3;12:e80122. doi: 10.7554/eLife.80122.


Peroxiredoxin 5 (Prdx5) is involved in pathophysiological regulation via the stress-induced cellular response. However, its function in the bone remains largely unknown. Here, we show that Prdx5 is involved in osteoclast and osteoblast differentiation, resulting in osteoporotic phenotypes in Prdx5 knockout (Prdx5Ko) male mice. To investigate the function of Prdx5 in the bone, osteoblasts were analyzed through immunoprecipitation (IP) and liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) methods, while osteoclasts were analyzed through RNA-sequencing. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) was identified as a potential binding partner of Prdx5 during osteoblast differentiation in vitro. Prdx5 acts as a negative regulator of hnRNPK-mediated osteocalcin (Bglap) expression. In addition, transcriptomic analysis revealed that in vitro differentiated osteoclasts from the bone marrow-derived macrophages of Prdx5Ko mice showed enhanced expression of several osteoclast-related genes. These findings indicate that Prdx5 might contribute to the maintenance of bone homeostasis by regulating osteoblast differentiation. This study proposes a new function of Prdx5 in bone remodeling that may be used in developing therapeutic strategies for bone diseases.

Keywords: bone regeneration; cell biology; developmental biology; mouse; osteoblast; osteoclast; osteoporosis; peroxiredoxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Regeneration
  • Cell Differentiation
  • Chromatography, Liquid
  • Heterogeneous-Nuclear Ribonucleoprotein K* / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein K* / metabolism
  • Male
  • Mice
  • Osteoblasts / metabolism
  • Osteoclasts / metabolism
  • Osteogenesis*
  • Tandem Mass Spectrometry


  • Heterogeneous-Nuclear Ribonucleoprotein K
  • Prdx5 protein, mouse

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.