Therapeutic Potential of SOX Family Transcription Factors in Osteoarthritis

Overview

Journal Ann Med

Publisher Informa Healthcare

Date 2025 Jan 31

PMID 39887675

Authors

Yue Huang

Zhuo Wang

Affiliations

Soon will be listed here.

Abstract

Background: As the worldwide population ages, osteoarthritis has significantly increased. This musculoskeletal condition has become a pressing global health issue and thus, prevention and treatment of osteoarthritis have become the primary focus of domestic and international research. Scholarly investigations of the molecular mechanisms that are related to the occurrence and development of osteoarthritis have shed light on the pathological causes of this condition to a certain extent, providing a foundation for its prevention and treatment. However, further research is necessary to fully understand the critical role of the transcription factor SOX9 in chondrocyte differentiation and the development of osteoarthritis. As a result, there has been widespread interest in SOX transcription factors. While SOX9 has been utilized as a biomarker to indicate the occurrence and prognosis of osteoarthritis, investigations into other members of the SOX family and the development of targeted treatments around SOX9 are still required.

Purpose: This article considers the impact of the SOX protein on the development and inhibition of osteoarthritis and highlights the need for therapeutic approaches targeting SOX9, as supported by existing research.

Results: SOX9 can contribute to the process of osteoarthritis through acetylation and ubiquitination modifications. The regulation of the WNT signalling pathway, Nrf2/ARE signalling pathway, NF-κB signalling pathway and SOX9 is implicated in the emergence of osteoarthritis. Non-coding RNA may play a role in the onset and progression of osteoarthritis by modulating various SOX family members, including SOX2, SOX4, SOX5, SOX6, SOX8, SOX9 and SOX11.

Conclusion: SOX9 has the capability of mitigating the onset and progression of osteoarthritis through means such as medication therapy, stem cell therapy, recombinant adeno-associated virus (rAAV) vector therapy, physical therapy and other approaches.

References

Xu F, Lv Y, Wang H, Song Y . miR-31-5p/SOX4 Axis Affects Autophagy and Apoptosis of Chondrocytes by Regulating Extracellular Regulated Protein Kinase/Mechanical Target of Rapamycin Kinase Signalling. Pathobiology. 2021; 89(2):63-73. DOI: 10.1159/000519006. View

Li Z, Wang X, Sun J, Wang Y, Wen Y, Tian W . [Effect of fire-needle intervention on joint function, cartilage impairment and inflammatory response in knee osteoarthritis rats]. Zhen Ci Yan Jiu. 2020; 45(3):220-6. DOI: 10.13702/j.1000-0607.190963. View

Zhang Y, Li R, Zhong Y, Zhang S, Zhou L, Shang S . Fuyuan Decoction Enhances SOX9 and COL2A1 Expression and Smad2/3 Phosphorylation in IL-1β-Activated Chondrocytes. Evid Based Complement Alternat Med. 2016; 2015:821947. PMC: 4685114. DOI: 10.1155/2015/821947. View

Zhang Y, Huang X, Yuan Y . Anti-inflammatory capacity of Apremilast in human chondrocytes is dependent on SOX-9. Inflamm Res. 2020; 69(11):1123-1132. DOI: 10.1007/s00011-020-01392-4. View

Wang Y, Li N, Wu X . Circular RNA_0003800 exacerbates IL-1β-induced chondrocyte injury via miR-197-3p/SOX5 axis. Int Immunopharmacol. 2023; 115:109643. DOI: 10.1016/j.intimp.2022.109643. View

Ma Z, Xu H, Xiang W, Qi J, Xu Y, Zhao Z . Deacetylation of FOXO4 by Sirt1 stabilizes chondrocyte extracellular matrix upon activating SOX9. Eur Rev Med Pharmacol Sci. 2021; 25(2):626-635. DOI: 10.26355/eurrev_202101_24621. View

Pereira D, Ramos E, Branco J . Osteoarthritis. Acta Med Port. 2015; 28(1):99-106. DOI: 10.20344/amp.5477. View

Iliopoulos D, Malizos K, Oikonomou P, Tsezou A . Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks. PLoS One. 2008; 3(11):e3740. PMC: 2582945. DOI: 10.1371/journal.pone.0003740. View

Zheng W, Feng Z, You S, Zhang H, Tao Z, Wang Q . Fisetin inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes through activating SIRT1 and attenuates the progression of osteoarthritis in mice. Int Immunopharmacol. 2017; 45:135-147. DOI: 10.1016/j.intimp.2017.02.009. View

10.

He J, Cao W, Azeem I, Shao Z . Epigenetics of osteoarthritis: Histones and TGF-β1. Clin Chim Acta. 2020; 510:593-598. DOI: 10.1016/j.cca.2020.08.011. View

11.

Zwickl H, Niculescu-Morzsa E, Halbwirth F, Bauer C, Jeyakumar V, Reutterer A . Correlation Analysis of SOX9, -5, and -6 as well as COL2A1 and Aggrecan Gene Expression of Collagen I Implant-Derived and Osteoarthritic Chondrocytes. Cartilage. 2016; 7(2):185-92. PMC: 4797238. DOI: 10.1177/1947603515615388. View

12.

Shi L, Zhang H, Sun J, Gao X, Liu C . CircSEC24A promotes IL-1β-induced apoptosis and inflammation in chondrocytes by regulating miR-142-5p/SOX5 axis. Biotechnol Appl Biochem. 2021; 69(2):701-713. DOI: 10.1002/bab.2145. View

13.

Liu X, Li X, Hua B, Yang X, Zheng J, Liu S . WNT16 is upregulated early in mouse TMJ osteoarthritis and protects fibrochondrocytes against IL-1β induced inflammatory response by regulation of RUNX2/MMP13 cascade. Bone. 2020; 143:115793. DOI: 10.1016/j.bone.2020.115793. View

14.

Sinclair A, Berta P, Palmer M, Hawkins J, GRIFFITHS B, Smith M . A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature. 1990; 346(6281):240-4. DOI: 10.1038/346240a0. View

15.

Ko J, Lee J, Lee J, Ryu Y, Im G . -, -Transfected Adipose Stem Cells to Treat Surgically-Induced Osteoarthritis in Goats. Tissue Eng Part A. 2018; 25(13-14):990-1000. DOI: 10.1089/ten.TEA.2018.0189. View

16.

Bai J, Zhang Y, Zheng X, Huang M, Cheng W, Shan H . LncRNA MM2P-induced, exosome-mediated transfer of Sox9 from monocyte-derived cells modulates primary chondrocytes. Cell Death Dis. 2020; 11(9):763. PMC: 7494881. DOI: 10.1038/s41419-020-02945-5. View

17.

Korogi W, Yoshizawa T, Karim M, Tanoue H, Yugami M, Sobuz S . SIRT7 is an important regulator of cartilage homeostasis and osteoarthritis development. Biochem Biophys Res Commun. 2018; . DOI: 10.1016/j.bbrc.2018.01.129. View

18.

Bastos R, Mathias M, Andrade R, Bastos R, Balduino A, Schott V . Intra-articular injections of expanded mesenchymal stem cells with and without addition of platelet-rich plasma are safe and effective for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2018; 26(11):3342-3350. DOI: 10.1007/s00167-018-4883-9. View

19.

Dai L, Zhang X, Hu X, Zhou C, Ao Y . Silencing of microRNA-101 prevents IL-1β-induced extracellular matrix degradation in chondrocytes. Arthritis Res Ther. 2012; 14(6):R268. PMC: 3674628. DOI: 10.1186/ar4114. View

20.

Wang Y, Chen Y, Wei Y . Osteoarthritis animal models for biomaterial-assisted osteochondral regeneration. Biomater Transl. 2023; 3(4):264-279. PMC: 9947734. DOI: 10.12336/biomatertransl.2022.04.006. View