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

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.