RESEARCH HIGHLIGHTS Nature Reviews Rheumatology | Published online 22 Jan 2016; doi:10.1038/nrrheum.2016.6 OSTEOARTHRITIS Osteophyte formation involves PAR2 Osteophytes, or bony spurs, are mineral density. Intra-articular bone outgrowths that form early injection of human PAR2-expressing fewer Par2-/- in osteoarthritis (OA) in an adenoviruses reversed the phenotype -/- mice developed attempt to compensate for joint of Par2 mice to control levels, damage. Huesa et al. now show that confirming that Par2 deletion is the osteophytes ... proteinase-activated receptor 2 causative factor. Histological analysis compared with (PAR2) is involved in this process, of the osteophytes in control mice control mice thereby expanding the known roles revealed the presence of proliferative of PAR2 in OA beyond cartilage and hypertrophic chondrocytes that degradation and osteosclerosis. expressed PAR2. Given that PAR2 is PAR2, a G protein-coupled not normally expressed in cartilage, receptor, might be involved in OA the authors concluded that expression through its role in modulating the of PAR2 in osteophytes is pathological. expression of metalloproteases. Carl Goodyear (co-corresponding Systemic inactivation of Par2 in author) also explains that they mice (Par2-/- mice) was previously used dynamic weight-bearing as a found to slow OA progression. surrogate indicator of pain, which is “In this study, we have a novel approach in OA models. integrated a cross-disciplinary range Par2-/- mice placed more weight on of techniques to allow an holistic the affected limb than controls, approach to elucidating early joint suggesting impaired nociception. changes in OA,” states John Lockhart, Taken together, these results co-corresponding author on this demonstrate that PAR2 is not only paper. Micro-CT showed that fewer involved in OA progression, but also Par2-/- mice developed osteophytes regulates early osteophyte formation 4 weeks after induction of OA via its presence in chondrocytes. through destabilization of the medial Moving forward, the authors will meniscus compared with control focus on the role of osteophyte mice; when osteophytes developed, formation in OA, a process that is they were smaller and had a greater not yet well understood. “Our work with PAR2 provides a means by which this process can be Osteophyte interrogated,” claims Lockhart. Liesbet Lieben, Associate Editor Nature Reviews Disease Primers PAR2 Chondrocyte ORIGINAL ARTICLE Huesa, C. et al. NPG Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology. Ann. Rheum. Dis. http://dx.doi.org/10.1136/ Bone annrheumdis-2015-208268 Nature Reviews | Rheumatology NATURE REVIEWS | RHEUMATOLOGY www.nature.com/nrrheum © 2016 Macmillan Publishers Limited. All rights reserved.