title: The hallmarks of osteoarthritis and the potential to develop personalised disease-modifying pharmacological therapeutics.
abstract: Osteoarthritis (OA) is an age-related condition and the leading cause of pain, disability and shortening of adult working life in the UK. The incidence of OA increases with age, with 25% of the over 50s population having OA of the knee. Despite promising preclinical data covering various molecule classes, there is regrettably at present no approved disease-modifying OA drugs (DMOADs). With the advent of next generation sequencing technologies, other therapeutic areas, in particular oncology, have experienced a paradigm shift towards defining disease by its molecular composition. This paradigm shift has enabled high resolution patient stratification and supported the emergence of personalised or precision medicines. In this review we evaluate the potential for the development of OA therapeutics to undergo a similar paradigm shift given that OA is increasingly being recognised as a heterogeneous disease affecting multiple joint tissues. We highlight the evidence for the role of these tissues in OA pathology as different "hallmarks" of OA biology and review the opportunities to identify and develop targeted disease-modifying pharmacological therapeutics. Finally, we consider whether it is feasible to expect the emergence of personalised disease-modifying medicines for patients with OA and how this might be achieved.
authors.affiliation: Faculty of Computing, Engineering and Sciences, Staffordshire University, Stoke-on-Trent ST4 2DF, UK. Electronic address: daniel.tonge@staffs.ac.uk.
authors.forename: D P
authors.initials: DP
authors.lastname: Tonge
authors.affiliation: MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity and Infection, University of Birmingham, Birmingham B15 2WB, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Pearson
authors.affiliation: MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity and Infection, University of Birmingham, Birmingham B15 2WB, UK. Electronic address: s.w.jones@bham.ac.uk.
authors.forename: S W
authors.initials: SW
authors.lastname: Jones
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000503:physiopathology; D057285:Precision Medicine / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal
keywords: OA; Osteoarthritis; Patient stratification; Personalised medicine