Table 2.

Effect of several endogenous proinflammatory substances on bone metabolism in RA and SpA.

Molecule	Disease	Effect on Bone Metabolism
TNF-α	RA and SpA	Binding to TNFR1: Promotion of osteoclastogenesis increasing RANKL expression in osteocytes [29,222] Promotion of osteoclastogenesis stimulating IL-1 secretion [29] Binding to TNFR2 (in SpA): In enthesis milieu, reduction of bone loss inhibiting osteoclasts’ activity [222]
IL-1	RA	Promotion of osteoclastogenesis acting on bone marrow-derived macrophages [29]
IL-6	RA	Promotion of osteoclastogenesis increasing RANKL expression in osteoblasts [85]
IL-17	✓RA ➢SpA	✓Promotion of osteoclastogenesis stimulating the production of other pro-inflammatory cytokines [24,94] and increasing RANK expression in osteoclasts precursors and RANKL secretion by osteocytes [157] ➢Promotion of the differentiation of osteoblasts precursors, synergistically with TNF-α [162]
IL-23	SpA	Stimulation of polarization into Th17. [182] Promotion of osteoclastogenesis increasing RANK expression in osteoclast precursors [27]
IL-22	SpA	Promotion of osteogenetic differentiation and migration of osteoblasts precursors synergistically with IFN-γ and TNF [234,235]

DKK-1: Dikkopf-1; FcγR, fc gamma receptor; IL: interleukin; RA: rheumatoid arthritis; RANK: receptor activator of NF-κB; RANKL: receptor activator of NF-κB ligand; SOST: sclerostin; SpA: spondyloarthritis; TNF-α: tumor necrosis factor-α; TNFR: tumor necrosis factor-α receptor; IFN-γ: Interferon gamma.