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

Abstract

AbstractPeroxiredoxin 5 (Prdx5) is involved in pathophysiological regulation via the stress-induced cellular response. However, the function of Prdx5 in the bone remains largely unknown. Here, we show that Prdx5 is involved in osteoclast and osteoblast differentiation, resulting in osteoporotic phenotypes inPrdx5knockout (Prdx5Ko) mice. Through immunoprecipitation and liquid chromatography combined with tandem mass spectrometry analysis, heterogeneous nuclear ribonucleoprotein K (hnRNPK) was identified as a potential binding partner of Prdx5 during osteoblast differentiationin vitro. We found that Prdx5 acts as a negative regulator of hnRNPK-mediated osteocalcin (Ocn) expression. In addition, transcriptomic analysis revealed thatin vitrodifferentiated osteoclasts from the bone marrow-derived macrophages ofPrdx5Komice 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.