Cysteine induces longitudinal bone growth in mice by upregulating IGF-I

Int J Mol Med. 2015 Aug;36(2):571-6. doi: 10.3892/ijmm.2015.2257. Epub 2015 Jun 23.

Abstract

Cysteine (Cys) is known to exert various effects, such as antioxidant, antipancreatitic and antidiabetic effects. However, the effects of Cys on longitudinal bone growth have not been elucidate to date. Thus, the aim of the present study was to evaluate the effects of Cys on bone growth. Growth-plate thickness and bone parameters, such as bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), connectivity density (Conn.D) and total porosity were analyzed by means of micro-computed tomography (μCT). The levels of serum insulin-like growth factor-I (IGF-I) were measured by enzyme-linked immunosorbent assay (ELISA). Hepatic IGF-I mRNA expression was analyzed by quantitative polymerase chain reaction (qPCR). The phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) was investigated by western blot analysis. Our results revealed that Cys increased IGF-I mRNA expression in HepG2 cells. The thickness of the growth plates was increased following treatment with Cys. Moreover, BV/TV, Tb.Th, TbN, Conn.D and total porosity were improved following treatment with Cys. Hepatic IGF-I mRNA expression and serum IGF-I levels were increased by Cys. The levels of phosphorylated JAK2 and STAT5 were elevated by Cys. The findings of our study indicate that Cys increases the thickness of growth plates through the upregulation of IGF-I, which results from the phosphorylation of JAK2-STAT5. Thus, our data suggest that Cys may have potential for use as a growth-promoting agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Development*
  • Bone and Bones / metabolism
  • Cysteine / metabolism*
  • Hep G2 Cells
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Janus Kinase 2 / metabolism
  • Liver / metabolism
  • Male
  • Mice
  • Phosphorylation
  • RNA, Messenger / genetics
  • STAT5 Transcription Factor / metabolism
  • Tibia / growth & development*
  • Tibia / metabolism
  • Up-Regulation*
  • X-Ray Microtomography

Substances

  • RNA, Messenger
  • STAT5 Transcription Factor
  • Insulin-Like Growth Factor I
  • Janus Kinase 2
  • Cysteine