Tenascin-C, a novel target to inhibit new bone formation in axial spondyloarthritis, linked with inflammation, mechanical strain and tissue damage

Axial spondyloarthritis is a chronic inflammatory musculoskeletal disease hallmarked by the paradoxical co-occurrence of inflammation, trabecular bone loss in the vertebrae and new bone formation with syndesmophyte growth potentially leading to spinal fusion or ankylosis. All these features can contribute to the burden of disease: pain, fatigue and loss of mobility and function.1 State of the art effective treatment strategies such as tumour necrosis factor (TNF) and interleukin (IL)-17 inhibitors focus on barring inflammation, but whether these approaches suffice to halt the bone remodelling aspects of the disease that determine the ultimate prognosis of patients is still debated.1 Long-term studies indicate that sustained suppression of inflammation impacts structural disease progression.2 Yet, the high individual variability in the ankylosis process suggests that there is an unmet need for early direct intervention in high risk or rapidly progressing patients.3 Anatomy and imaging studies demonstrate that spinal ankylosis originates from pathological changes in the enthesis, the insertion sites of ligaments and tendons onto the bone. Former studies highlighted how growth factor pathways that are essential in skeletal development and growth, are inappropriately reactivated in the ankylosis process.4 5 However, targeting signalling systems such as the bone morphogenetic protein and Wnt cascades comes with important considerations about impact on other tissues and organs. More attractive therapeutic targets may be found in earlier and specific disease processes, an area that remains largely unexplored. In this journal, Li et al identify tenascin-C (TNC) as a key driver of new bone formation originating from the enthesis, and mechanistic experiments intriguingly position this extra-cellular matrix molecule as a converging node between inflammation, mechanical strain, tissue damage and new bone formation.6 TNC is a glycoprotein with a number of remarkable features as extensively discussed by Midwood et al . …