A hallmark of spondylarthropathies (SpA), such as ankylosing spondylitis, (AS) is the fusion of joints as well as intervertebral spaces. This fusion is caused by the formation of bony spurs appearing as syndesmophytes and osteophytes in the intervertebral spaces and in the joints, respectively. Fusion of joints is based on increased endochondral ossification, which allows bone formation and bridges the joint space. Tumour necrosis factor (TNF) is a key proinflammatory cytokine in AS, but is a potent inhibitor of bone formation, and so is unlikely to explain the formation of osteophytes in AS. This is also suggested by recent clinical data showing that TNF blockade seems not to affect structural remodeling of the spinal skeleton in AS, which largely indicates changes due to increased bone apposition. Thus, molecular concepts of structural remodelling in AS need revision, and new pathways involved in bone formation, such as Wingless proteins or transforming growth factor β, might be a clue to the pathogenesis of structural remodelling in AS. The efficacy of TNF blockers to improve clinical symptoms in AS, their poor effect on structural remodelling, and the weak relationship between clinical symptoms and structural damage in AS will profoundly revise our picture of AS in the future.

MECHANISMS OF JOINT FORMATION—MOLECULAR LESSONS FOR JOINT FUSION

Joints and intervertebral spaces form gaps between bones, which allow motion and flexibility. These gaps are actively formed during early development, when chondrogenic formations of the vertebral column and limbs start to branch and build segments. Formation of these gaps depends on the expression of proteins involved in mesenchymal cell differentiation, such as cartilage-derived morphogenic protein 1 (also called GDF5) and bone morphogenic protein (BMP) 5.¹ Without these proteins no joints are formed, since the appropriate differentiation of cells, which form the synovial membrane, are …