Table 1.

Summary of the cytokine effects on osteoblasts and osteoclasts.

Cytokine	Effects on osteoblasts	Effects on osteoclasts	References
TNF-α	stimulate osteoblasts to express RANKL and M-CSF low concentration stimulates mesenchymal precursor cell differentiation into osteoblasts while high concentration inhibits osteoblasts’ function and bone formation inhibit IGF-1 and RUNX2 expression to suppress osteoblast differentiation	stimulate osteoclast differentiation promote RANK expression in osteoclast precursors promote RANKL-induced osteoclastogenesis induce osteoclast precursors to express c-Fos	(9–12, 13–15)
IL-1α	–	stimulate the formation of OLC	(16)
IL-1β	induce bone resorption in osteoblasts by activating p38 MAPK inhibit human osteoblast migration	activate osteoclasts and stimulate osteoclast differentiation, multinucleation, and survival	(17–20, 21, 22)
IL-3	increase osteoblast differentiation and matrix mineralization promote the expression of osteoblast-specific genes	inhibit RANKL-induced osteoclast differentiation inhibit TNF-induced osteoclast differentiation, bone resorption inhibit blood monocytes and bone marrow cells differentiate into osteoclasts	(23–29)
IL-4	–	directly and indirectly suppress osteoclastogenesis inhibit the bone resorption activity of mature, differentiated osteoclasts	(30–37)
IL-6	inhibit osteoblast differentiation	directly and indirectly stimulate osteoclast formation inhibit osteoclast progenitors to differentiate into osteoclasts	(38–43, 44, 45)
OSM	promote stromal cells to differentiate into osteoblast	stimulate RANKL production and osteoclast formation	(41, 46, 47)
IL-7	–	promote osteoclast formation by inducing T cells to produce RANKL and TNF-α promote bone resorption by inducing B cells increase stimulate osteoclast formation by activating STAT5	(48–50)
IL-8	–	promote RANKL-induced osteoclastogenesis	(51)
IL-10	inhibit bone marrow osteogenic activity	inhibit osteoclast progenitors differentiate into osteoclast precursors inhibit RANK-induced osteoclast formation	(52–56)
IL-11	extend the survival of osteoblast progenitor cells promote pluripotent progenitor cells to differentiate into osteoblast lineage promote osteogenesis, inhibit adipogenesis and sclerostin in osteoblasts	stimulate osteoclast differentiation and osteoclast formation	(38, 57–59, 46, 60)
IL-12	–	inhibit RANKL-induced osteoclastogenesis through inhibiting NFATc1 or promotion of osteoblast apoptosis via the Fas/FasL	(61, 62)
IL-13	–	inhibit osteoclast formation and bone resorption	(36, 63)
IL-15	promote osteoblast apoptosis	promote osteoclast progenitors to differentiate into osteoclast precursor induce osteoclast formation	(64–66)
IL-17	promote the expression of pro-osteoclastic cytokines such as TNF-α, IL-6, and RNAKL in osteoblasts promote osteoblast differentiation while inhibiting osteoblast calcification	induce osteoclastogenesis low concentrations promote autophagy of osteoclast precursors and osteoclast formation while high concentrations inhibit osteoclast precursors’ differentiation into osteoclasts	(67–79)
IL-18	–	inhibit TNF-α-induced osteoclastogenesis by mediating myeloid apoptosis via Fas/FasL and NO indirectly inhibit osteoclast formation via IFN-γ and GM-CSF	(80–84)
IL-19	–	inhibit RANKL-induced osteoclast differentiation maintain the osteoclast precursor state	(85)
IL-20	upregulate RANKL expression in osteoblasts inhibit osteoblasts survival and differentiation	induce the expression of RANK in M-CSF-derived osteoclast precursors and promote the transduction of osteoclastic signals	(86, 87)
IL-23	–	participate in T-cell-mediated osteoclast formation modulate osteoclast differentiation indirectly inhibit osteoclast formation	(88–91)
IL-27	inhibit osteoblast apoptosis	inhibit osteoclastogenesis	(92–95)
IL-29	–	inhibit osteoclast formation and bone resorption activity	(96, 97)
IL-32	promote bone formation and prevent bone loss	–	(98)
IL-33	stimulate osteoblast function promote matrix mineral deposition and reduces sclerostin mRNA	inhibit RANKL-induced osteoclast formation and osteoblast-related gene expression induce osteoclasts apoptosis inhibit TNF-induced osteoclast formation and bone resorption	(99–101, 102, 103)
IL-34	regulate hBMSC osteogenesis and enhance fracture healing	induce osteoclast differentiation and bone resorption promote the proliferation and differentiation of BMMs toward osteoclasts	(104–106)
IL-35	stimulate MSCs to differentiate into osteoblasts	prevent TNF-induced osteoclast formation and promote apoptosis promote functional osteoclast formation increase osteoclast differentiation factors expression	(107–109)
IL-37	increase the expression of osteoblast-specific genes promote osteogenic differentiation of MSCs	inhibit osteoclast formation and pathological bone resorption	(110, 111)
IFN-α	–	inhibit RANKL-induced osteoclastogenesis by reducing c-Fos	(112, 113)
IFN-β	–	inhibit RANKL-induced osteoclastogenesis by reducing c-Fos inhibit osteoclastogenesis by increasing NO production and the iNOS signaling pathway	(112–114)
IFN-γ	stimulate osteoblast differentiation genes expression stimulate osteoblast differentiation	inhibit osteoclast differentiation and function mediate osteoclast apoptosis via Fas/FasL	(115–121)