Effects of Gymnema Sylvestre on the post-transcriptional processing of the RANK -encoded RNA: A Possible Treatment for Osteoporosis

Abstract

According to the National Institute of Health, half of women and a quarter of men will break a bone due to osteoporosis, a disease categorized by low bone density. Bone density and strength are regulated by two types of cells, osteoclasts, which dissolve bone, and osteoblasts which build bone. If the balance between osteoclasts and osteoblasts is disturbed, a diseased state will occur. While osteoporosis is caused by a relative increase in osteoclast activity, osteopetrosis, a genetic disease categorized by extremely high bone density, is caused by a decrease in osteoclast activity. It has been suggested that environmental factors may influence osteoclast and osteoblast function. Through the use of a variety of chemical compounds, one can endeavor to manipulate the transcription or post-transcriptional modification of RNA transcripts critical to the functioning of osteoclasts, thereby compromising osteoclast function and enhancing bone density. HL-60 and THP1 cell lines were treated with various nutraceuticals and screened for possible transcriptional/posttranscriptional changes in gene-encoded transcripts critical to osteoclast function. Both RTPCR and qRT-PCR analysis has demonstrated that treatment of cells with extracts generated from Gymnema Sylvestre results in a post-transcriptional modification that results in the generation of an alternatively spliced transcript form of the transcript encoded by the RANK gene. As mutations in the RANK gene that compromise the functionality of this gene product have been demonstrated to cause osteopetrosis, through its effect on osteoclast differentiation and survival, it is believed that Gymnema Sylvestre extract may be able to compromise osteoclast function and be used as a treatment for osteoporosis.