Table 1.
Roles of cytokines and miRNA.
| Names | Functions | References | ||
|---|---|---|---|---|
| IL | ||||
| IL-4 | prevents bone damage | (Freire et al., 2021) | ||
| IL-12 | (1)increases MMP-1, MMP-3 and MMP-13; (2)inhibits MMP-2 and MMP-9 | (Ma et al., 2017; Miao et al., 2017) | ||
| IL-17 | (1)up-regulates RANKL through the JAK2-STAT3 pathway;(2)promotes osteoclast differentiation | (Wang Z et al., 2018; Xiong et al., 2019; Wei et al., 2021) | ||
| IL-17a | (1)recruiting neutrophils | (Ferreira et al., 2016) | ||
| IL-10 | (1)inhibits RANKL expression;(2)inhibits osteoclast differentiation;(3)up-regulates OPG | (Duka et al., 2019; Wei et al., 2021) | ||
| IL-22 | bone destruction | (de Oliveira et al., 2015) | ||
| IL-34 | binds to RANKL and stimulates osteoclast formation | (Ma et al., 2016) | ||
| IL-33 | (1)higher concentration of IL-33 up-regulates RANKL;(2)lower levels of IL-33 up-regulates OPG | (Duka et al., 2019) | ||
| IL-1β | bone resorption(osteoclast formation) | (1)increases the levels of IL-17A, IL-17F, IL-21, and IL-22;(2)pathologically up-regulates the expressions of IFN-γ and GM-CSF | (Ma et al., 2017; Veloso et al., 2020; Zhang Z et al., 2020; Hasiakos et al., 2021) | |
| IL-6 | (1)promotes the expression of RANKL;(2)promote functional osteoclast differentiation | |||
| IL-23 | stimulates osteoclast formation in LPS-induced PDL cells | |||
| IL-21 | :: | |||
| IFN | ||||
| IFN-γ | (1)up-regulates RANKL;(2)attenuates the promoting effect of IL-17 on gene expression of Alp, Runx2, Osteocalcin, OPG and RANKL;(3)promotes early differentiation of osteoblasts, but negatively modulates osteoblast calcification | (Wang Z et al., 2018; Wobma et al., 2018; Duka et al., 2019) | ||
| IFN-α | anti-osteoblast cytokines | (Amarasekara et al., 2021) | ||
| IFN-β | strong inhibitor of osteoclast formation | (Zheng et al., 2017; Amarasekara et al., 2021) | ||
| IFN-λ1 | inhibits osteoclast formation | (Chen et al., 2020) | ||
| CSF | ||||
| MCSF | facilitates the proliferation process of osteoclast precursor cells and helps maintain the survival of osteoclasts | impacts macrophage | (Anesi et al., 2019) | |
| GCSF | (1)increases the expression of inflammatory factors such as CXC chemokines, interleukins (IL-1β, IL-6) and MMP-9;(2)up-regulates the ratio of RANKL/OPG and the number of osteoclasts | (Zhang Z et al., 2020) | ||
| TNF | ||||
| TNF-α | (1)activates osteoclasts and inhibits collagen synthesis;(2)directly affects osteoblast expression of osteolytic cytokines through NF-κB signaling pathway;(3)up-regulates M-CSF to indirectly affects osteoclast formation and activity;(4)up-regulates the release of prostaglandin E2 from osteoblasts;(5)alleviates bone loss via up-regulating exosome CD73 expression and inducing polarization of M2 macrophages;(6)promotes RANKL expression and promotes osteoclast differentiation | promotes functional osteoclast differentia -tion | (Yu et al., 2016; Wang et al., 2017; Canalis et al., 2021; Wei et al., 2021) | |
| TNF-β | activates osteoclasts and inhibits collagen synthesis | |||
| miRNA | ||||
| mir-10A-5p | down-regulates TNF-A mRNA levels and up-regulates IL-10 | (Shen et al., 2021) | ||
| mir-155 | inhibits SEMA3A | (Yue et al., 2016) | ||
| mir-335-5p | (1)promotes the expression of RANKL in HPDLFs;(2)inhibits uPAR;(3)promotes osteogenic differentiation in mice | (Yue et al., 2017; Zhang et al., 2017) | ||
| mir-200a | takes parts in migration of bone marrow mesenchymal stem cells | (Li et al., 2020) | ||
| mir-181b-5p | (1)promotes osteoblast apoptosis;(2)modulates the NF-κB signaling pathway | (Wang et al., 2019; Lv et al., 2020) | ||
| mir-146a | negatively regulates the expression of IL-6, IL-1β and TNF-α | (Lina et al., 2019) | ||
| mir-1260b | inhibits osteoclast formation through the WNT5a-mediated RANKL pathway | (Nakao et al., 2021) | ||