Extracellular Signal-Regulated Kinases Play Essential but Contrasting Roles in Osteoclast Differentiation
Abstract
1. Bone Homeostasis
2. OC Formation and Function
2.1. Formation of OCs
2.2. Characteristics of OCs
2.3. Bone Resorption by OCs
3. BMM-Derived OCs and RAW 264.7-Derived OCs
4. Role of MAPKs in OC Differentiation
5. Role of ERKs in OC Differentiation
5.1. Similarities and Differences between ERK1 and ERK2
5.2. ERK1/2 in OC Differentiation
6. The Positive Role of ERK1/2 in OC Differentiation
7. The Negative Role of ERK1/2 in OC Differentiation
8. ERK5 in OC Differentiation
9. p38 MAPK and JNK in OC Differentiation
10. Conclusions
Funding
Informed Consent Statement
Conflicts of Interest
References
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BMM-OC | RAW-OC | References | |
---|---|---|---|
v-Abl expression | No | Yes | [29,30] |
Cytokine requirement for differentiation | M-CSF and RANKL | RANKL | [3,31,34,35] |
Increased gene expression | ACTC1, AP-1, ATP6v0d2, CAH, CARD10, COF2, CTSK, ENDOG, FN1, GIT1, ITGAV, ITGβ3, JUNB, MCL1, MMP9, MYP2, NFATc1, NF-κB2, OSCAR, PXN, RPA2, RRAS, SRC, TPM2, TRAP | ATP6v0d2, AP-1, CAH, CDK6, DAP12, FRA2, GAB2, GSN, ITGAX, JUNB, MCM3 and -5, MMP9, NFATc1, PCNA, POLD1, RELA, SRC, TRAP | [33] |
Decreased gene expression | BLNK, CDC2, CDK1, ERK1, FCRγ, c-FMS, IQGAP2, ITGA6, LIG1, MCM2, -3, and -4, NFATc2, NF-κB1, PCNA, POLE3, p90RSK, RELA, RPA1 and -3, TK1, TREM2 | BLNK, FCRγ, c-FMS, PI3K | [33] |
Apoptosis at 5 days 16 h | 78% | 42% | [33] |
ERK inhibition | inhibits OC differentiation | [35,36,37,38] | |
inhibits OC differentiation | [39] | ||
enhances OC differentiation | [35,40,41,42] |
ERK Isoforms | Other Names | Gene Names (Human) | Gene Names (Mouse) | Inhibitors | |
---|---|---|---|---|---|
Typical ERKs | ERK1 | MAPK3, p44 MAPK | MAPK3 | Mapk3 | FR180204, LY3214996 (Temuterkib), PD0325091, PD0325901 (Mirdametinib), PD98059, Selumetinib, U0126 |
ERK2 | MAPK1, p42 MAPK | MAPK1 | Mapk1 | FR180204, LY3214996, PD0325091, PD0325901, PD98059, Selumetinib, U0126 | |
ERK5 | BMK1, MAPK7 | MAPK7 | Mapk7 | BIX02188, BIX02188, XMD8-92 | |
Atypical ERKs | ERK3 | ERK6, MAPK6, MAPK12 | MAPK6, MAPK12 | Mapk4 | |
ERK4 | MAPK4, p63 MAPK | MAPK4 | Mapk4 | ||
ERK7/8 | MAPK15 | MAPK15 | Mapk15 (rat) |
ERK Isoforms | Cells | Cytokines | Methods | Effect on OC Formation | OC-Specific Gene Expression | References |
---|---|---|---|---|---|---|
ERK1/2 | BMMs | M-CSF + RANKL | Gene deletion | ERK1: positive ERK2: ns * | [65] | |
ERK1/2 | BMMs | M-CSF + RANKL | PD98059, U0126 | ERK1/2: positive | [35] | |
ERK1/2 | BMMs | M-CSF + RANKL | PD0235901 | ERK1/2: positive | ACP5, V-ATPase D2, CTSK, DC-STAMP, c-Fos, NFATc1 | [67] |
ERK1/2 | BMMs | M-CSF + RANKL | PD98059 | ERK1/2: no effect | [68] | |
ERK2 | RAW 264.7 | RANKL | ERK2 siRNA | ERK2: negative | CTSK, DC-STAMP, NFATc1 | [35] |
ERK1/2 | RAW 264.7 | M-CSF + RANKL | PD98059 | ERK1/2: no effect | [68] | |
ERK1/2 | RAW 264.7 | RANKL | PD98059, U0126 | ERK1/2: negative | CTR, CTSK, DC-STAMP, NFATc1, TRAP | [40] [42] [35] |
ERK1/2 | RAW 264.7 | M-CSF + RANKL | U0126 | ERK1/2: ns | [41] | |
ERK1/2 | RAW 264.7 | RANKL | FR180204 | ERK1/2: positive | upregulation: CTSK (ns), TRAF6 (ns) downregulation: DC-STAMP, MMP9, NFATc1, TRAP | [39] |
PD98059 | upregulation: NFATc1 (ns), TRAP (ns) downregulation: CTSK (ns), MMP9 (ns) |
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Kim, C. Extracellular Signal-Regulated Kinases Play Essential but Contrasting Roles in Osteoclast Differentiation. Int. J. Mol. Sci. 2023, 24, 15342. https://doi.org/10.3390/ijms242015342
Kim C. Extracellular Signal-Regulated Kinases Play Essential but Contrasting Roles in Osteoclast Differentiation. International Journal of Molecular Sciences. 2023; 24(20):15342. https://doi.org/10.3390/ijms242015342
Chicago/Turabian StyleKim, Chaekyun. 2023. "Extracellular Signal-Regulated Kinases Play Essential but Contrasting Roles in Osteoclast Differentiation" International Journal of Molecular Sciences 24, no. 20: 15342. https://doi.org/10.3390/ijms242015342
APA StyleKim, C. (2023). Extracellular Signal-Regulated Kinases Play Essential but Contrasting Roles in Osteoclast Differentiation. International Journal of Molecular Sciences, 24(20), 15342. https://doi.org/10.3390/ijms242015342