Ghrelin up-regulates cartilage-specific genes via the ERK/STAT3 pathway in chondrocytes of patients with adolescent idiopathic scoliosis

Biochem Biophys Res Commun. 2019 Oct 15;518(2):259-265. doi: 10.1016/j.bbrc.2019.08.044. Epub 2019 Aug 14.


Adolescent idiopathic scoliosis (AIS) is a severe spinal deformity that often occurs during puberty. The occurrence of AIS is suggested to be related to abnormal development of cartilage. Our previous study found increased serum ghrelin levels in AIS patients that may linked to the development of AIS. However, whether ghrelin affects cartilage in AIS patients is unclear. We used quantitative real-time PCR (qRT-PCR) and immunohistochemistry to detect the expression of cartilage-specific genes and the ghrelin receptor, growth hormone secretagogue receptor (GHSR). The mRNA and protein levels of collagen II (COLII), SOX9, AGGRECAN (ACAN) and GHSR were higher in AIS patients than in controls. In addition, the protein levels of GHSR downstream signaling pathway members p-STAT3 (Ser727), and p-ERK1/2 were increased. Furthermore, we treated chondrocytes from AIS patients with 100 nM ghrelin, the cell proliferation assay and Western blotting showed that ghrelin promotes chondrocyte proliferation and enhances COLII, SOX9, ACAN, p-ERK1/2 and p-STAT3 expression, respectively. Interestingly, all these observed alterations were abolished by ghrelin + [D-Lys3]-GHRP-6 (a ghrelin receptor inhibitor) treatment. And after U0126 (an inhibitor of ERK1/2 phosphorylation) treatment, ERK1/2 and STAT3 (Ser727) phosphorylation was simultaneously suppressed indicating that ERK1/2 is an upstream pathway protein of STAT3 (Ser727). In conclusion, ghrelin plays an important role in upregulating cartilage-specific genes on AIS primary chondrocytes by activating ERK/STAT3 signaling pathway.

Keywords: Adolescent idiopathic scoliosis; Chondrocyte; ERK1/2; GHSR; Ghrelin; STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aggrecans / genetics
  • Aggrecans / metabolism
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Child
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Ghrelin / pharmacology*
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • SOX9 Transcription Factor / genetics
  • SOX9 Transcription Factor / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Scoliosis / drug therapy*
  • Scoliosis / metabolism
  • Scoliosis / pathology
  • Up-Regulation / drug effects*
  • Up-Regulation / genetics*


  • ACAN protein, human
  • Aggrecans
  • Collagen Type II
  • Ghrelin
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human