The Effect of Long-Term Exercise on the Production of Osteoclastogenic and Antiosteoclastogenic Cytokines by Peripheral Blood Mononuclear Cells and on Serum Markers of Bone Metabolism

Table 2

Modulation of bone and immune cells by cytokines.

Cytokine	Osteoblast	Osteoclast	Osteocyte	Bone (in vitro)	Rodents (in vivo)	T cells, B cells, and macrophages	References
IL1-α/β	↑ RANKL	↓ apoptosis		↑ resorption			[2–8, 15, 16]
TNF-α	↑ RANKL	↓ apoptosis; ↑ RANKL-independent osteoclastogenesis		↑ resorption; ↓ formation			[2–8, 16–18]
IFN-γ		↓ RANKL signaling pathways		↓ collagen synthesis	↑ bone loss; ↓ osteopetrosis; ↓ bone loss	↑ TNF-α, RANKL	[19–26]
IL-4	↓ RANKL; ↑ OPG					↑ Th2-type; ↓ Th1-type	[27–29]
Il-6	↑ RANKL; ↑ precursors; ↓ apoptosis	↓ RANKL; signaling pathways	↑ production with loading			↓ TNF-α, IL-1α/β; ↑ IL-4, IL-10, IL-1ra, OPG, and B cell maturation	[30–42]
Il-10	↑ OPG	↓ RANKL signaling pathways			↓ bone loss	↓ IFN-γ, IL-1α/β, TNF-α, and T helper cell proliferation	[43–46]
TGF-β	↓ RANKL,; ↑ OB differentiation and synthesis of OPG and osteoid matrix	↓ osteoid; degrading; enzymes; ↑ Wnt1	↑ production with loading	↑ osteoid matrix		↓ TNF-α, IL-1α/β, and IFN-γ	[41, 47–51]

RANKL, receptor activator of nuclear factor kappa B ligand, promoting osteoclastogenesis by binding to RANK on osteoclast precursors. OPG, osteoprotegerin; a decoy RANKL receptor & potent inhibitor of osteoclastogenesis. Wnt1, a protein crucial to normal bone formation. IL-1ra, interleukin-1 receptor antagonist.