Novel insights into the effect of deer IGF-1 on chondrocyte viability and IL-1β-induced inflammation response

J Biochem Mol Toxicol. 2023 Jan;37(1):e23227. doi: 10.1002/jbt.23227. Epub 2022 Sep 29.

Abstract

Clinical treatment of Osteoarthritis (OA) remains a challenge due to the poor self-regeneration ability of cartilage. Deer antler is the only cartilage tissue that can completely regenerate each year. Insulin-like growth factor 1 (IGF-1) is one of the major active components in the deer antler that participate in regulating the rapid regeneration of deer antler cartilage. This has led us to speculate that deer IGF-1 might potentially become a candidate drug for reducing damage and inflammation of OA. Thus, we aimed to explore the underlying mechanism of deer IGF-1 in chondrocyte proliferation, differentiation, and inflammation response. Deer, mouse, and human IGF-1 amino acid sequences and protein structures were aligned using CLUSTAL and PSIPRED. The underlying molecular mechanism of deer IGF-1 on primary chondrocytes was investigated by RNA-sequencing (RNA-seq) technology combined with various experiments. Cytokine interleukin-1β (IL-1β) was used to induce the inflammation response of primary chondrocytes. We found that deer IGF-1 was more similar to human IGF-1 than mouse IGF-1. qRT-PCR and immunofluorescence assay indicated that deer IGF-1 had stronger effects than mouse IGF-1. We also found that the deer IGF-1 enhanced the expression of cell proliferation, differentiation, and extracellular matrix (ECM)-related genes, but decreased the expression of ECM-degrading genes. Deer IGF-1 also attenuated the IL-1β-induced inflammatory and ECM degradation in chondrocytes. This study provides insight into the molecular mechanisms of deer IGF-1 on primary chondrocyte viability and presents a candidate for combatting inflammatory responses in OA development.

Keywords: Osteoarthritis; RNA-seq; cell proliferation and differentiation; deer IGF-1; primary chondrocyte.

MeSH terms

  • Animals
  • Apoptosis
  • Chondrocytes / metabolism
  • Deer* / genetics
  • Deer* / metabolism
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology
  • Mice
  • MicroRNAs* / metabolism
  • Osteoarthritis* / metabolism

Substances

  • Interleukin-1beta
  • Insulin-Like Growth Factor I
  • MicroRNAs