Kruppel-like Factors in Skeletal Physiology and Pathologies
Abstract
:1. Skeletal Development and Maintenance
2. Krüppel in Drosophila
3. Kruppel-like Factors in Vertebrates
4. Roles of KLFs in Normal Bone Physiology (Table 1)
4.1. KLF1
4.2. KLF2
4.3. KLF3
4.4. KLF4
4.5. KLF5
4.6. KLF6
4.7. KLF7
4.8. KLF8
4.9. KLF9
4.10. KLF10
4.11. KLF11
Factors | Phenotypes | Studies |
---|---|---|
KLF1 | Growth defects (LOF in human; unlikely cell-autonomous actions) | [36,37,38,39] |
KLF2 | Abnormal craniofacial morphogenesis (LOF in mouse) | [42] |
KLF3 | High bone mass (LOF in human; by mutated lncRNA) | [46] |
KLF4 | High bone mass with increased osteoclast differentiation (osteoblast-specific LOF in mouse) Repressed osteoclast maturation (osteoblast-specific GOF in mouse) | [55] [57] |
KLF5 | Retarded skeletal growth with delayed primary ossification center formation (LOF in mouse) | [71] |
KLF6 | Remain to be investigated | – |
KLF7 | High bone mineral density associated with its low expression (in human) | [81] |
KLF8 | Remain to be investigated | – |
KLF9 | Remain to be investigated | – |
KLF10 | Growth defect with suppressed cartilage maturation and primary ossification center formation | [102,103] |
KLF11 | None | [114] |
KLF12 | Remain to be investigated (in vitro studies exist) | – |
KLF13 | Remain to be investigated (in vitro studies exist) | – |
KLF14 | Remain to be investigated (in vitro studies exist) | – |
KLF15 | Remain to be investigated (in vitro studies exist) | – |
KLF16 | Remain to be investigated (in vitro studies exist) | – |
KLF17 | Remain to be investigated | – |
4.12. KLF12
4.13. KLF13
4.14. KLF14
4.15. KLF15
4.16. KLF16
4.17. KLF17
5. Role of KLFs in Osteoarthritis, Osteoporosis, and Osteosarcoma
5.1. Osteoarthritis
5.2. Osteoporosis
5.3. Bone Tumors
Factors | Conclusion | Studies | |
---|---|---|---|
Osteoarthritis | KLF2 KLF4 KLF5 KLF15 | Downregulated in OA patients Represses IL1β-induced MMP13 expression Suppresses ROS production Downregulated in human OA samples Induces PRG4 and collagen genes Downregulated in human OA samples Downregulated in human OA samples | [133,134,135,136,137,138,139] [140,141] [136,141] [135,136] |
Osteoporosis | KLF3 KLF4 KLF10 | Endothelial cell-specific KO mice show high bone mass Osteoblast-specific KO mice show high bone mass Osteoprogenitor-specific KO mice show low bone mass Downregulated in osteoporotic patients Downregulated in ovariectomy rats Female Klf10 KO mice show reduced bone strength | [46] [54,60] [103,166,167] |
Osteosarcoma | KLF2 KLF4 KLF5 KLF6 KLF8 KLF9 KLF11 | Downregulated in OS cells in vitro Induces cancer stemness Highly expressed in OS cells ML264 (KLF5 inhibitor) induces OS cell activation Downregulated in OS cells Highly expressed in OS samples Induces cancer stemness Downregulated in OS cells Downregulated in OS samples Suppresses cancer stem cell induction | [181] [183,184] [192,193] [194] [185,186] [194] [186,191] |
6. Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Abe, M.; Saeki, N.; Ikeda, Y.; Ohba, S. Kruppel-like Factors in Skeletal Physiology and Pathologies. Int. J. Mol. Sci. 2022, 23, 15174. https://doi.org/10.3390/ijms232315174
Abe M, Saeki N, Ikeda Y, Ohba S. Kruppel-like Factors in Skeletal Physiology and Pathologies. International Journal of Molecular Sciences. 2022; 23(23):15174. https://doi.org/10.3390/ijms232315174
Chicago/Turabian StyleAbe, Makoto, Naoya Saeki, Yuki Ikeda, and Shinsuke Ohba. 2022. "Kruppel-like Factors in Skeletal Physiology and Pathologies" International Journal of Molecular Sciences 23, no. 23: 15174. https://doi.org/10.3390/ijms232315174