Long noncoding RNAs: a missing link in osteoporosis

Osteoporosis is a systemic disease that results in loss of bone density and increased fracture risk, particularly in the vertebrae and the hip. This condition and associated morbidity and mortality increase with population ageing. Long noncoding (lnc) RNAs are transcripts longer than 200 nucleotides that are not translated into proteins, but play important regulatory roles in transcriptional and post-transcriptional regulation. Their contribution to disease onset and development is increasingly recognized. Herein, we present an integrative revision on the studies that implicate lncRNAs in osteoporosis and that support their potential use as therapeutic tools. Firstly, current evidence on lncRNAs involvement in cellular and molecular mechanisms linked to osteoporosis and its major complication, fragility fractures, is reviewed. We analyze evidence of their roles in osteogenesis, osteoclastogenesis, and bone fracture healing events from human and animal model studies. Secondly, the potential of lncRNAs alterations at genetic and transcriptomic level are discussed as osteoporosis risk factors and as new circulating biomarkers for diagnosis. Finally, we conclude debating the possibilities, persisting difficulties, and future prospects of using lncRNAs in the treatment of osteoporosis. Molecular biology: decoding the dark matter of osteoporosis Genomic ‘dark matter’ could improve the diagnosis and prognosis of patients with osteoporosis, as well as providing new drug targets for the disease. Only 2.3% of the human genome is translated into protein; the function of the remainder had been unclear, but recent studies suggest some of it provides instructions for making regulators of protein synthesis called long non-coding RNAs (lncRNAs). In this review, Maria Ines Almeida at the University of Porto in Portugal and colleagues explore the role of lncRNAs in bone cell differentiation, metabolism and fracture healing - and describe early studies assessing their role as diagnostic and prognostic biomarkers of osteoporosis. Future advances in genome editing may also provide opportunities to redress the balance between bone production and resorption – something that becomes skewed in osteoporosis - by targeting lncRNAs.