Reduced TIPE2 expression is inversely associated with proinflammatory cytokines and positively correlated with bone mineral density in patients with osteoporosis

Life Sci. 2019 Jan 1:216:227-232. doi: 10.1016/j.lfs.2018.11.054. Epub 2018 Nov 27.

Abstract

Aims: The tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) participates in multiple inflammatory diseases. However, its underlying mechanism in osteoporosis has not been elucidated. The aim of current study is to preliminarily clarify the function of TIPE2 in the pathogenesis of osteoporosis.

Main methods: TIPE2 expression in patients with osteoporosis was measured by Western blot and qRT-PCR methods. Proinflammatory cytokines including TNF-α, IL-1 and IL-6 were assessed via enzyme-linked immunosorbent assay. Serum fasting PINP and β-CTX were measured by the chemiluminescence method. Simple logistic regression analysis was performed for the odds ratio (OR) for TIPE2.

Key findings: TIPE2 expression in patients with osteoporosis was dramatically decreased and negatively correlated with proinflammatory cytokines. Furthermore, TIPE2 level was negatively correlated with fasting β-CTX, but not PINP, indicating that TIPE2 participates in the pathogenesis of osteoporosis dominantly by supression of bone resorption. Interestingly, TIPE2 expression level was positively correlated with bone mineral density (BMD), and its expression level can predict the risk of bone fracture using the simple logistic regression assay.

Significance: Our findings clarify that TIPE2 alleviates the pathogenesis of osteoporosis by suppressing the inflammatory status and the ability of TIPE2 for predicts bone fracture further demonstrated that TIPE2 might serve as a novel diagnostic marker and a therapeutic target for osteoporosis.

Keywords: BMD; Osteoporosis; Proinflammatory cytokines; TIPE2.

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Bone Density / genetics*
  • Case-Control Studies
  • Cytokines / blood*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-1 / blood
  • Interleukin-6 / blood
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Logistic Models
  • Male
  • Middle Aged
  • Osteoporosis / genetics
  • Osteoporosis / physiopathology*
  • Osteoporotic Fractures / epidemiology*
  • Osteoporotic Fractures / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • TNFAIP8L2 protein, human
  • Tumor Necrosis Factor-alpha