UNDERSTANDING THE CONTRIBUTION OF A LNCRNA DURING THE EARLY STAGES OF OSTEOGENESIS

Long non-coding RNAs (lncRNAs) are transcripts of greater than 200 nucleotides with no protein coding potential that can regulate gene expression or protein function and coordinate cellular processes such as development, differentiation, and disease including cancer. The goal of this study is to determine the function and mechanism of a newly discovered long non-coding RNA (called lncRNA-1) in regulating osteogenic differentiation. While there is compelling data on the role of lncRNAs in other cellular systems (such as cancer), there is a significant gap in our understanding of how lncRNAs function in bone biology. To date, there is very little information on how lncRNAs affect osteoblast differentiation either functionally or mechanistically. We have previously generated RNA-seq libraries from mouse pre- osteoblastic cells induced to osteoblastic differentiation. Detailed analysis of this RNA-Seq data has shown that thirty-one lncRNAs exhibit a dynamic expression pattern. From these, nine lncRNAs were subsequently chosen for further study based on novelty (not previously annotated) and significant changes in their expression levels during early phases of osteogenesis. We showed that knock-down of one of these lncRNAs (lncRNA-1) inhibits osteogenic differentiation in mouse primary osteoblastic cells. Based on this result, we hypothesize that lncRNA-1, plays an essential role in regulating osteogenesis. By determining its function during osteogenesis, insight into the molecular mechanisms controlling osteogenic commitment of pre-osteoblastic cells will be gained.