Runx2 and Polycystins in Bone Mechanotransduction: Challenges for Therapeutic Opportunities

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 May 25

PMID 38791330

Authors

Antonios N Gargalionis

Christos Adamopoulos

Christos T Vottis

Athanasios G Papavassiliou

Efthimia K Basdra

Affiliations

Soon will be listed here.

Abstract

Bone mechanotransduction is a critical process during skeletal development in embryogenesis and organogenesis. At the same time, the type and level of mechanical loading regulates bone remodeling throughout the adult life. The aberrant mechanosensing of bone cells has been implicated in the development and progression of bone loss disorders, but also in the bone-specific aspect of other clinical entities, such as the tumorigenesis of solid organs. Novel treatment options have come into sight that exploit the mechanosensitivity of osteoblasts, osteocytes, and chondrocytes to achieve efficient bone regeneration. In this regard, runt-related transcription factor 2 (Runx2) has emerged as a chief skeletal-specific molecule of differentiation, which is prominent to induction by mechanical stimuli. Polycystins represent a family of mechanosensitive proteins that interact with Runx2 in mechano-induced signaling cascades and foster the regulation of alternative effectors of mechanotransuction. In the present narrative review, we employed a PubMed search to extract the literature concerning Runx2, polycystins, and their association from 2000 to March 2024. The keywords stated below were used for the article search. We discuss recent advances regarding the implication of Runx2 and polycystins in bone remodeling and regeneration and elaborate on the targeting strategies that may potentially be applied for the treatment of patients with bone loss diseases.

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References

Ziros P, Rojas Gil A, Georgakopoulos T, Habeos I, Kletsas D, Basdra E . The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells. J Biol Chem. 2002; 277(26):23934-41. DOI: 10.1074/jbc.M109881200. View

Khonsari R, Ohazama A, Raouf R, Kawasaki M, Kawasaki K, Porntaveetus T . Multiple postnatal craniofacial anomalies are characterized by conditional loss of polycystic kidney disease 2 (Pkd2). Hum Mol Genet. 2013; 22(9):1873-85. DOI: 10.1093/hmg/ddt041. View

Yang D, Okamura H, Nakashima Y, Haneji T . Histone demethylase Jmjd3 regulates osteoblast differentiation via transcription factors Runx2 and osterix. J Biol Chem. 2013; 288(47):33530-33541. PMC: 3837102. DOI: 10.1074/jbc.M113.497040. View

Merrick D, Mistry K, Wu J, Gresko N, Baggs J, Hogenesch J . Polycystin-1 regulates bone development through an interaction with the transcriptional coactivator TAZ. Hum Mol Genet. 2018; 28(1):16-30. PMC: 6298236. DOI: 10.1093/hmg/ddy322. View

Duplomb L, Droin N, Bouchot O, Thauvin-Robinet C, Bruel A, Thevenon J . A constitutive BCL2 down-regulation aggravates the phenotype of PKD1-mutant-induced polycystic kidney disease. Hum Mol Genet. 2017; 26(23):4680-4688. DOI: 10.1093/hmg/ddx349. View

Lee P, Heinemann C, Zheng K, Appali R, Alt F, Krieghoff J . The interplay of collagen/bioactive glass nanoparticle coatings and electrical stimulation regimes distinctly enhanced osteogenic differentiation of human mesenchymal stem cells. Acta Biomater. 2022; 149:373-386. DOI: 10.1016/j.actbio.2022.06.045. View

Dalagiorgou G, Piperi C, Georgopoulou U, Adamopoulos C, Basdra E, Papavassiliou A . Mechanical stimulation of polycystin-1 induces human osteoblastic gene expression via potentiation of the calcineurin/NFAT signaling axis. Cell Mol Life Sci. 2012; 70(1):167-180. PMC: 5012114. DOI: 10.1007/s00018-012-1164-5. View

Kim H, Park J, Lee K, Yoon H, Shin D, Ju U . Plant homeodomain finger protein 2 promotes bone formation by demethylating and activating Runx2 for osteoblast differentiation. Cell Res. 2014; 24(10):1231-49. PMC: 4185351. DOI: 10.1038/cr.2014.127. View

Lu J, Shi X, Fu Q, Li Y, Zhu L, Lu N . MicroRNA-584-5p/RUNX family transcription factor 2 axis mediates hypoxia-induced osteogenic differentiation of periosteal stem cells. World J Stem Cells. 2023; 15(10):979-988. PMC: 10631372. DOI: 10.4252/wjsc.v15.i10.979. View

10.

Wang D, Cai J, Zeng Z, Gao X, Shao X, Ding Y . The interactions between mTOR and NF-κB: A novel mechanism mediating mechanical stretch-stimulated osteoblast differentiation. J Cell Physiol. 2020; . DOI: 10.1002/jcp.30184. View

11.

Hajarnis S, Patel V, Aboudehen K, Attanasio M, Cobo-Stark P, Pontoglio M . Transcription Factor Hepatocyte Nuclear Factor-1β (HNF-1β) Regulates MicroRNA-200 Expression through a Long Noncoding RNA. J Biol Chem. 2015; 290(41):24793-805. PMC: 4598991. DOI: 10.1074/jbc.M115.670646. View

12.

Sun H, Li Q, Lv X, Ai J, Yang Q, Duan J . MicroRNA-17 post-transcriptionally regulates polycystic kidney disease-2 gene and promotes cell proliferation. Mol Biol Rep. 2009; 37(6):2951-8. DOI: 10.1007/s11033-009-9861-3. View

13.

Wang L, Lu Y, Cai G, Chen H, Li G, Liu L . Polycystin-2 mediates mechanical tension-induced osteogenic differentiation of human adipose-derived stem cells by activating transcriptional co-activator with PDZ-binding motif. Front Physiol. 2022; 13:917510. PMC: 9450996. DOI: 10.3389/fphys.2022.917510. View

14.

Katsianou M, Papavassiliou K, Zoi I, Gargalionis A, Panagopoulos D, Themistocleous M . Polycystin-1 modulates RUNX2 activation and osteocalcin gene expression via ERK signalling in a human craniosynostosis cell model. J Cell Mol Med. 2021; 25(7):3216-3225. PMC: 8034462. DOI: 10.1111/jcmm.16391. View

15.

Mevel R, Draper J, Lie-A-Ling M, Kouskoff V, Lacaud G . RUNX transcription factors: orchestrators of development. Development. 2019; 146(17). DOI: 10.1242/dev.148296. View

16.

Komori T . Whole Aspect of Runx2 Functions in Skeletal Development. Int J Mol Sci. 2022; 23(10). PMC: 9144571. DOI: 10.3390/ijms23105776. View

17.

Gargalionis A, Korkolopoulou P, Farmaki E, Piperi C, Dalagiorgou G, Adamopoulos C . Polycystin-1 and polycystin-2 are involved in the acquisition of aggressive phenotypes in colorectal cancer. Int J Cancer. 2014; 136(7):1515-27. DOI: 10.1002/ijc.29140. View

18.

Wildman B, Godfrey T, Rehan M, Chen Y, Afreen L, Hassan Q . MICROmanagement of Runx2 Function in Skeletal Cells. Curr Mol Biol Rep. 2019; 5(1):55-64. PMC: 6615570. DOI: 10.1007/s40610-019-0115-4. View

19.

Lu W, Shen X, Pavlova A, Lakkis M, Ward C, Pritchard L . Comparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects. Hum Mol Genet. 2001; 10(21):2385-96. DOI: 10.1093/hmg/10.21.2385. View

20.

Takata S, Yasui N . Disuse osteoporosis. J Med Invest. 2001; 48(3-4):147-56. View