Development of a Mouse Model of Enthesis‐Specific NF‐κB Activation

Enthesitis, or inflammation specific to sites in the body where tendon inserts into bone, can arise in isolated joints from overuse or in multiple joints as a complication of an autoimmune condition such as psoriatic arthritis or spondyloarthritis. However, the pathogenesis of enthesitis is not well understood, so treatment strategies are limited. A clinically relevant animal model of enthesitis would allow investigators to determine mechanisms driving the disease and evaluate novel therapies. Therefore, we developed a murine model of inducible enthesis-specific inflammation by constitutively activating the NF-κB pathway in Gli1+ cells. Gli1Cre^ERT mice were crossed with IKKβ-overexpression mice and given tamoxifen injections 5 days postnatally to induce enthesitis. Sixteen weeks of IKKβ overexpression in enthesis cells led to impaired mechanical properties, subtle histologic changes, and changes to expression of extracellular matrix- and inflammation-related genes. Increased loading from treadmill overuse activity did not exacerbate this phenotype. Clinical significance: The new murine model may have utility for studying the pathogenesis of enthesitis and approaches to treat the condition.