Aberrant bone formation and dysregulated bone homeostasis in ankylosing spondylitis

Table 1 Mechanisms of osteoclast dysregulation in ankylosing spondylitis

Category	Molecular mechanism	Effect on osteoclasts	Ref.
Inflammatory cytokines	TNF-α, IL-17, IL-23, IL-6	Promotes osteoclast differentiation and activation	[2-4]
RANK/RANKL/OPG pathway	Increases RANKL expression and decreases OPG	Enhances osteoclast formation and bone resorption	[1,3]
TNF-α signaling	Activates NF-κB and MAPK pathways	Enhances osteoclast survival and activity	[2-4]
T-helper cells	Secrete IL-17 and IL-23	Stimulates RANKL production and osteoclastogenesis	[2,8,14]
Wnt/β-catenin signaling	Inhibited by DKK-1 and sclerostin	Reduces bone formation, favors resorption	[3,8,10]
Bone resorption factors	MMPs, CatK	Degrades the bone matrix, increasing erosion	[8,10]

TNF-α: Tumor necrosis factor-alpha; IL: Interleukin; RANK: Receptor activator of nuclear factor-kappa B; RANKL: Receptor activator of nuclear factor-kappa B ligand; OPG: Osteoprotegerin; NF-κB: Nuclear factor-kappa B; MAPK: Mitogen-activated protein kinases; Wnt/β: Wingless-related integration site/beta; DKK-1: Dickkopf-related protein 1; MMPs: Matrix metalloproteinases; CatK: Cathepsin K.