Cytokine-Mediated Bone Destruction in Rheumatoid Arthritis

Table 1

Roles of cytokines on osteoclastogenesis.

	In Vitro	In Vivo
TNF-α	Osteoclastogenic; (i) Upregulates the expression of RANKL and osteoclast activators; (ii) Enhances osteoclast differentiation synergistically with RANKL or independently of RANKL; (iii) Inhibits osteoclast apoptosis	Osteoclastogenic; (i) Upregulates the expression of RANKL and osteoclast activators; (ii) Induces osteoclastogenesis in the presence or absence of RANKL; (iii) Plays a critical role in inflammatory arthritis; (iv) Associated with estrogen-deficient osteoporosis and joint destruction in RA
	References: [12, 21, 110–116]	References: [15, 24, 36, 117–119]
IL-1	Osteoclastogenic; (i) Upregulates the expression of RANKL and osteoclast activators; (ii) Enhances osteoclast differentiation synergistically with RANKL or independently of RANKL	Osteoclastogenic; (i) Induces osteoclastogenesis in the presence or absence of RANKL; (ii) Mediates TNF--induced osteoclastogenesis; (iii) Participates in physiological bone metabolism; (iv) Associated with estrogen-deficient osteoporosis
	References: [33, 35, 116, 120–122]	References: [23, 29–32, 36, 37]
IL-6	Osteoclastogenic; (i) Upregulates the expression of RANKL and osteoclast activators; (ii) Induces RANKL-dependent osteoclastogenesis	Osteoclastogenic; (i) Enhances osteoclastogenesis in the prepubertal stage; (ii) Supports osteoclastogenesis in callus formation during fracture healing; (iii) Associated with bone loss from inflammatory arthritis and estrogen deficiency
	References: [10, 44, 123–129]	References: [46, 48, 49, 130–132]
	Antiosteoclastogenic; (i) Suppresses the RANK signaling pathway; (ii) Diverts cells into the macrophage lineage	Antiosteoclastogenic; (i) Suppresses the differentiation of early osteoclast precursor cells; (ii) Decreases osteoclast formation, leading to reduced bone turnover
	References: [6, 133, 134]	References: [46, 47, 135]
IL-17	Osteoclastogenic; (i) Induces the expression of RANKL and proinflammatory cytokines; (ii) Increases sensitivity to RANKL; (iii) Enhances osteoclastogenesis via prostaglandin E2 (PGE2) in osteoblasts	Osteoclastogenic; (i) Induces the expression of RANKL and proinflammatory cytokines; (ii) Mediates estrogen-deficient osteoporosis
	References: [1, 53, 136–141]	References: [52, 142–144]
	Anti-osteoclastogenic; (i) Suppresses osteoclast formation at high concentrations; (ii) Inhibits osteoclastogenesis by induction of GM-CSF
	References: [145, 146]
IL-23	Osteoclastogenic; Induces osteoclastogenesis via IL-17	Osteoclastogenic; (i) Induces the expression of RANKL; (ii) Expands myeloid-lineage osteoclast precursors
	References: [56]	References: [65, 147–150]
	Antiosteoclastogenic; Inhibits osteoclast formation via T cells	Antiosteoclastogenic; Limits the resorption of immature bone below the growth plate
	References: [57, 151]	References: [57]