Table 1 Diverse agents that regulate RANKL/RANK signaling pathway in osteolclastogenesis

ISO

Inhibited the combination of RANKL/RANK

hPDLCs (human)

BMMs (C57BL/6 mice)

C57BL/6 mice

10–50 μM

2–10 μM

10 mg/kg

Fan et al. (2023), Li et al. (2023)

Niloticin

Blocked the interaction between RANKL and RANK

RAW264.7 cell

N/A

2.5–7.5 μM

N/A

Xu et al. (2022)

EGCG

Disrupted the interaction between RANKL and RANK

RAW264.7 cell

N/A

10–50 μM

N/A

Xu et al. (2021)

EA

Interfered with the interaction between RANKL and RANK

RAW264.7 cell

N/A

1–8 μM

N/A

Xu et al. (2020)

Denosumab

Blocked the RANKL/RANK signaling pathway

BMMs (C3H/HeN mice)

BDF1 mice

50 pM

0.2, 1.0, 5.0 mg/kg

Kostenuik et al. (2009)

IL-20 inhibitors

Inhibited the interaction between RANKL and IL-20

BMMs (Sprague–Dawley rats)

Sprague–Dawley rats

0–20 ng/mL

N/A

Meng et al. (2023)

Rab11b

Eliminated the surface abundance of RANK on osteoclast precursor cells

RAW-D cells

BMMs (C57BL/6 mice)

N/A

10 pM

N/A

Tran et al. (2020)

TRAF-STOP

Inhibited TRAF6 expression

BMMs (C57BL/6 mice)

C57BL/6 mice

1 μM

N/A

Huang et al. (2023)

Curcumin

Inhibited TRAF6 expression

preosteoclasts (human)

BMMs (C57BL/6 mice)

Tg-hRANKL mice

1–10 μM

15 nM

200 mg/kg

Ke et al. (2023), von Metzler et al. (2009)

As

Decreased TRAF6 expression

RAW264.7 cell

Wistar rats

0.1–10 μM

2.5, 5, 10 mg/kg

Nie et al. (2023)

RANK-tet

Targeted the RANK binding region of TRAF-C

BMMs (C57BL/6 mice)

N/A

10 μg/mL

N/A

Anzai et al. (2022)

TA

Suppressed TRAF6 and NFATc1 expression

RAW264.7 cell

N/A

2.5–7.5 μM

N/A

Liu et al. (2022a)

Mogrol

Blocked TRAF6 activations and decreased NFATc1 expression

BMMs (C57BL/6 mice)

C57BL/6 mice

5–20 μM

10 mg/kg

Chen et al. (2022b)

CUL

Blocked the binding of IPMK to TRAF6

BMMs (C57BL/6 mice)

C57BL/6 mice

25–100 μM

2.5, 10 mg/kg

Wang et al. (2021)

l-THP

Blocked the interaction between RANK and TRAF6

RAW264.7 cell

BMMs (C57BL/6 mice)

C57BL/6 mice

4.75–19.00 μg/mL

N/A

Zhi et al. (2020)

PFD

Decreased the effectiveness of NF-κB activation and inhibited NF-κB expression

BMMs (C57BL/6 mice)

C57BL/6 mice

200–800 μM

60, 120 mg/kg

Zhang et al. (2023b)

Saf

Interfered with NF-κB signaling

BMMs (C57BL/6 mice)

C57BL/6 mice

5–20 μM

10, 20 mg/kg

Sheng et al. (2023)

SR

Mediated NF-κB pathway-dependent autophagy

BMMs (Sprague–Dawley rats)

Sprague–Dawley rats

2 mM

900 mg/kg

Wu et al. (2023)

EPZ015866

Blocked the demethylation of NF-κB p65 subunit

RAW264.7 cell

BMMs (C57BL/6 mice)

N/A

20–1000 nM

N/A

Ding et al. (2023)

Surfactin

Regulated NF-κB signaling pathway

BMMs (C57BL/6 mice)

C57BL/6 mice

10–1000 nM

4, 20 mg/kg

Kuang et al. (2023)

Isopsoralen

Suppressed NF-κB signaling pathway

Jawbone marrow mesenchymal cells (human)

BMMs (C57BL/6 mice)

N/A

1 μM

10–30 μM

N/A

Zhan et al. (2023), Zhu et al. (2023)

AL

Inhibited NF-κB signaling pathway

RAW264.7 cell

BMMs (C57BL/6 mice)

C57BL/6 mice

10–300 μM

1.25, 5 mg/kg

Zhuang et al. (2023)

DIC

Inhibited the activity of Nrf2 and NF-κB

RAW264.7 cell

C57BL/6 mice

50–150 μM

10, 20 mg/kg

Wong et al. (2022)

Elt

Blocked the translocation of IκBα and NF-κB p65

BMMs (C57BL/6 mice)

C57BL/6 mice

25–100 nM

0.075, 0.15 mg/kg

Chen et al. (2022a)

PTX

Blocked MAPK and Ca²⁺-calcineurin-NFATc1 signaling pathways

BMMs (C57BL/6 mice)

C57BL/6 mice

5–20 μM

5, 10 mg/kg

Sun et al. (2023)

Citropten

Inhibited MAPK and PLCγ/Ca²⁺ signaling pathways

RAW264.7 cell

N/A

5–40 μM

N/A

Trang et al. (2023)

ORI

Inhibited MAPK/NF-κB pathway and activated intracellular ROS generation

RAW264.7 cell

BMMs (SD rats)

N/A

3.38 μM

N/A

Jin et al. (2023b)

FMN

Suppressed MAPK signaling pathway

BMMs (C57BL/6 mice)

C57BL/6 mice

5–40 μM

10, 20 mg/kg

Ni et al. (2023); Yu et al. (2023b)

Iss

Inhibited MAPK signaling pathway

BMMs (C57BL/6 mice)

C57BL/6 mice

1–10 μM

5, 10 mg/kg

Qin et al. (2023)

BML-111

Reduced the activation of MAPK pathways

BMMs (C57BL/6 mice)

C57BL/6 mice

25–100 μM

1 mg/kg

Wang et al. (2023b)

TSN

Interfered with p38 subunit activation and regulated the MAPK cascade

RAW264.7 cell

BMMs (C57BL/6 mice)

C57BL/6 mice

2–8 nM

0.3, 0.6 mg/kg

Tan et al. (2023)

PD0325901

Inhibited ERK activation

BMMs (C57BL/6 mice)

C57BL/6 mice

0.32–1.28 nM

5, 10 mg/kg

Jiang et al. (2023)

AST

Negatively regulated MAPK signaling

MH7A cells (human)

BMMs (C57BL/6 mice)

C57BL/6 mice

50–200 μM

50–100 μM

20 mg/kg

Jia et al. (2019), Xing et al. (2022)

GSK 650394

Inhibited the activation of MAPK signaling pathway

BMMs (C57BL/6 mice)

C57BL/6 mice

1–5 μM

10, 30 mg/kg

Jin et al. (2022)

Met

Suppressed ERK phosphorylation

BMMs (C57BL/6 mice)

N/A

200–400 μM

N/A

Chen et al. (2022c)

TPB

Blocked MAPK and NF-κB signaling pathways

BMMs (C57BL/6 mice)

C57BL/6 mice

1–10 μM

1 mg/kg

Wang et al. (2022d)

KYMASIN UP

Reduced p38 MAPK activation

RAW264.7 cell

N/A

12.5–100 μg/mL

N/A

Salvadori et al. (2022)

Neratinib

Inhibited the MAPK pathway

BMMs (C57BL/6 mice)

C57BL/6 mice

3.13–12.5 nM

5, 10 mg/kg

Qiu et al. (2022)

DHD

Suppressed MAPK and Ca²⁺signaling pathway

BMMs (C57BL/6 mice)

C57BL/6 mice

0.25–2 μM

2 mg/kg

He et al. (2022b)

EMCL

Inhibited the phosphorylation of ERK1/2

BMMs (C57BL/6 mice)

C57BL/6 mice

0.625–2.5 μM

2.5 mg/kg

Long et al. (2022)

ZOL

Reduced c-Jun and c-Fos expression

RAW264.7 cell

N/A

0.1–5 μM

N/A

Huang et al. (2022)

LLLI

Decreased c-Jun and c-Fos expression

N/A

Sprague–Dawley rats

N/A

N/A

Zhang et al. (2020)