Hwanggeumchal sorghum extract enhances BMP7 and GH signaling through the activation of Jak2/STAT5B in MC3T3‑E1 osteoblastic cells

Mol Med Rep. 2013 Sep;8(3):891-6. doi: 10.3892/mmr.2013.1593. Epub 2013 Jul 18.

Abstract

Sorghum is a principal cereal food in a number of parts of the world and is critical in folk medicine in Asia and Africa. However, its effects on bone are unknown. Growth hormone (GH) is a regulator of bone growth and bone metabolism. GH activates several signaling pathways, including the Janus kinase (Jak)/signal transducer and activator of transcription (STAT) pathways, thereby regulating expression of genes, including insulin‑like growth factor (IGF)‑1. Bone morphogenetic proteins (BMPs) induce the differentiation of cells of the osteoblastic lineage, increasing the pool of IGF‑1 target cells, the mature osteoblasts. In the present study, the effects of Hwanggeumchal sorghum extracts (HSE) on GH signaling via the Jak/STAT pathway in osteoblasts were investigated. HSE was not observed to be toxic to osteoblastic cells and increased the expression of BMP7 and GH‑related proteins, including STAT5B, p‑STAT5B, IGF‑1 receptor (IGF-1R), growth receptor hormone (GHR) and Jak2 in MC3T3‑E1 cells. In addition, HSE increased BMP7 and GHR mRNA expression in MC3T3‑E1 cells. The expression of HSE‑induced BMP7 and GHR was inhibited by AG490, a Jak2 kinase inhibitor. The observations indicate that HSE‑induced signaling is similar to GH signaling via the GHR‑Jak2 signaling axis. Using small interference RNA (siRNA) analysis, STAT5B was found to play an essential role in HSE‑induced BMP7 and GH signaling in MC3T3‑E1 cells. Results of the current study indicate that HSE promotes bone growth through activation of STAT5B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 7 / genetics
  • Bone Morphogenetic Protein 7 / metabolism*
  • Cell Differentiation
  • Cell Line
  • Cell Lineage
  • Gene Expression / drug effects
  • Growth Hormone / metabolism*
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / metabolism*
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / toxicity*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Receptor, IGF Type 1 / metabolism
  • Receptors, Somatotropin / genetics
  • Receptors, Somatotropin / metabolism
  • STAT5 Transcription Factor / antagonists & inhibitors
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction / drug effects*
  • Sorghum / chemistry
  • Sorghum / metabolism*
  • Tyrphostins / pharmacology

Substances

  • Bone Morphogenetic Protein 7
  • Plant Extracts
  • RNA, Small Interfering
  • Receptors, Somatotropin
  • STAT5 Transcription Factor
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • Growth Hormone
  • Receptor, IGF Type 1
  • Janus Kinase 2