Fig. 5

Early, intermediate and late phases of disease progression are delineated by inflammation, excessive tissue and ectopic chondrocyte formation. a Unsupervised clustering differentiates the model into three stages corresponding with disease duration. The x-axis depicts the time points of the mice. The left box (stage 1), middle box (stage 2) and right box (stage 3) represent early, intermediate and late stages of disease development, respectively. Scores for (b) inflammation, (c) excessive tissue formation and (d) ectopic chondrocyte formation are distinct between these three groups. e Axial disease was initially characterised by transient inflammation that included vertebral joint infiltration by monocular cells, activation of tissue remodelling (matrix metalloproteinases, or MMPs) and pro-arthritic inflammatory pathways (tumour necrosis factor, or TNF). Vertebral joint inflammation culminated in destructive changes, including destruction of the intervertebral disc, the latter of which was irreparable and would have considerable impact on joint biomechanics. In advanced disease, inflammation is decreased; however, excessive tissue and ectopic chondrocyte formation driven by chondroidal ossification was the predominant feature and occurred only in joints in which the IVD had been severely compromised