Progranulin Protects Against Osteonecrosis of the Femoral Head by Activating ERK1/2 Pathway

Inflammation. 2017 Jun;40(3):946-955. doi: 10.1007/s10753-017-0539-z.

Abstract

The aim of this study was to investigate progranulin (PGRN) expression and its effect in cartilage degradation and in the pathogenesis of osteonecrosis of the femoral head (ONFH). Cartilage specimens were obtained from ONFH and FNF patients and PGRN expression was analyzed by immunohistochemistry, western blot analysis, and RT-PCR. Peripheral blood PGRN level was detected by ELISA. Additionally, primary chondrocytes were cultured and treated with PGRN. Next, the expression of aggrecan and collagen II and the activation of ERK1/2 were detected. We observed that the expression of PGRN was significantly upregulated in ONFH patients' articular cartilage, and recombinant PGRN could promote expression of aggrecan and collagen II and the activation of ERK1/2. Collectively, PGRN can improve chondrocyte anabolism and perform a therapeutic role in the pathogenesis of ONFH. This study helps to elucidate the pathogenesis of ONFH and presents PGRN as a potential target for the treatment of ONFH.

Keywords: ERK; TNF-α; osteonecrosis; progranulin.

MeSH terms

  • Aggrecans / metabolism
  • Cartilage, Articular
  • Cells, Cultured
  • Chondrocytes / metabolism
  • Collagen / metabolism
  • Femur Head / pathology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood
  • Intercellular Signaling Peptides and Proteins / physiology*
  • MAP Kinase Signaling System / drug effects*
  • Osteonecrosis / prevention & control*
  • Progranulins
  • Protective Agents / pharmacology

Substances

  • Aggrecans
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • Protective Agents
  • Collagen