The emerging role of lncRNAs in osteoarthritis development and potential therapy

Osteoarthritis (OA) is the most common joint disorder, is associated with an increasing socioeconomic impact owing to the ageing population and mainly affects the diarthrodial joints. Primary OA results from a combination of risk factors, with increasing age and obesity being the most prominent. The concept of the pathophysiology is still evolving, from being viewed as cartilage-limited to a multifactorial disease that affects the whole joint. An intricate relationship between local and systemic factors modulates its clinical and structural presentations, leading to a common final pathway of joint destruction. Pharmacological treatments are mostly related to relief of symptoms and there is no disease-modifying OA drug (that is, treatment that will reduce symptoms in addition to slowing or stopping the disease progression) yet approved by the regulatory agencies. Identifying phenotypes of patients will enable the detection of the disease in its early stages as well as distinguish individuals who are at higher risk of progression, which in turn could be used to guide clinical decision making and allow more effective and specific therapeutic interventions to be designed. This Primer is an update on the progress made in the field of OA epidemiology, quality of life, pathophysiological mechanisms, diagnosis, screening, prevention and disease management.

Therapeutic targeting of noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), represents an attractive approach for the treatment of cancers, as well as many other diseases. Over the past decade, substantial effort has been made towards the clinical application of RNA-based therapeutics, employing mostly antisense oligonucleotides and small interfering RNAs, with several gaining FDA approval. However, trial results have so far been ambivalent, with some studies reporting potent effects whereas others demonstrated limited efficacy or toxicity. Alternative entities such as antimiRNAs are undergoing clinical testing, and lncRNA-based therapeutics are gaining interest. In this Perspective, we discuss key challenges facing ncRNA therapeutics — including issues associated with specificity, delivery and tolerability — and focus on promising emerging approaches that aim to boost their success. Over the past decade, several RNA-based therapies have gained FDA approval. Additional noncoding RNA (ncRNA)-based therapeutic approaches — targeting microRNAs and long ncRNAs — are now also gaining interest. Here, Calin and co-authors assess the hurdles facing the clinical translation of ncRNA-based therapeutics and highlight promising emerging solutions to address these issues.