Epigenetic Control of Osteogenesis: Pathways Toward Improved Bone Regeneration

Wu C-H, Tu S-T, Chang Y-F, Chan D-C, Chien J-T, Lin C-H, Singh S, Dasari M, Chen J-F, Tsai K-S. Fracture liaison services improve outcomes of patients with osteoporosis-related fractures: A systematic literature review and meta-analysis. Bone. 2018;111:92–100.

Article  PubMed  Google Scholar 

Chuang P-Y, Yang T-Y, Tsai Y-H, Huang K-C. Do NSAIDs affect bone healing rate, delay union, or cause non-union: an updated systematic review and meta-analysis. Front Endocrinol. 2024. https://doi.org/10.3389/fendo.2024.1428240.

Article  Google Scholar 

Ghanem W, Ezzeddine H, Saad R, et al. State of the nonunion: A review of the latest literature. Orthop Rev (Pavia). 2025;17:129085.

Article  PubMed  Google Scholar 

Wu AM, Bisignano C, James SL, Abady GG, Abedi A, Abu-Gharbieh E, et al. Global, regional, and National burden of bone fractures in 204 countries and territories, 1990–2019: a systematic analysis from the global burden of disease study 2019. Lancet Healthy Longev. 2021;2(9):e580–92.

Article  Google Scholar 

Quan K, Xu Q, Zhu M, Liu X, Dai M. Analysis of risk factors for Non-union after surgery for limb fractures: A Case-Control study of 669 subjects. Front Surg. 2021. https://doi.org/10.3389/fsurg.2021.754150.

Article  PubMed  PubMed Central  Google Scholar 

Huo R, Wei C, Huang X, et al. Mortality associated with osteoporosis and pathological fractures in the united States (1999–2020): a multiple-cause-of-death study. J Orthop Surg Res. 2024;19:568.

Article  PubMed  PubMed Central  Google Scholar 

Tran T, Ho-Le T, Bliuc D, Abrahamsen B, Hansen L, Vestergaard P, Center JR, Nguyen TV. Skeletal age’ for mapping the impact of fracture on mortality. eLife. 2023;12:e83888.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aranguren S, Cole H, Dargan LJ, Sarlo M, Choi S, Satapathy I, De Vasconcellos JF. Recent advances in the regulatory and non-coding RNA biology of osteogenic differentiation: biological functions and significance for bone healing. Front Cell Dev Biol. 2025;12:1483843.

Article  PubMed  PubMed Central  Google Scholar 

Howard K, Ferris WF, Van De Vyver M. The characterization and comparison of femoral bone-derived skeletal stem cells. Biochimie. 2025;233:88–98.

Article  CAS  PubMed  Google Scholar 

Zhu S, Chen W, Masson A, Li Y-P. Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis. Cell Discov. 2024;10:1–39.

Article  Google Scholar 

Yoon H, Park SG, Shin H-R, Kim K-T, Cho Y-D, Moon J-I, Kim W-J, Ryoo H-M. Unraveling the dynamics of osteoblast differentiation in MC3T3-E1 cells: transcriptomic insights into matrix mineralization and cell proliferation. Bone. 2025;194:117442.

Article  CAS  PubMed  Google Scholar 

Lin X, Patil S, Gao Y-G, Qian A. The bone extracellular matrix in bone formation and regeneration. Front Pharmacol. 2020. https://doi.org/10.3389/fphar.2020.00757.

Article  PubMed  PubMed Central  Google Scholar 

Donsante S, Palmisano B, Serafini M, Robey PG, Corsi A, Riminucci M. From stem cells to Bone-Forming cells. IJMS. 2021;22:3989.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Walewska A, Janucik A, Tynecka M, Moniuszko M, Eljaszewicz A. Mesenchymal stem cells under epigenetic control– the role of epigenetic machinery in fate decision and functional properties. Cell Death Dis. 2023;14:720.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li Q, Xu R, Lei K, Yuan Q. Insights into skeletal stem cells. Bone Res. 2022;10(1):61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang F, Xu L, Xu L, Xu Q, Karsenty G, Chen CD. Histone demethylase JMJD3 is required for osteoblast differentiation in mice. Sci Rep. 2015;5:13418.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ye L, Fan Z, Yu B, Chang J, Al Hezaimi K, Zhou X, Park N-H, Wang C-Y. Histone demethylases KDM4B and KDM6B promotes osteogenic differentiation of human MSCs. Cell Stem Cell. 2012;11:50–61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ghorbaninejad M, Khademi-Shirvan M, Hosseini S, Baghaban Eslaminejad M. Epidrugs: novel epigenetic regulators that open a new window for targeting osteoblast differentiation. Stem Cell Res Ther. 2020;11:456.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li K, Han J, Wang Z. Histone modifications centric-regulation in osteogenic differentiation. Cell Death Discov. 2021;7(1):91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Montecino M, Carrasco ME, Nardocci G. Epigenetic control of osteogenic lineage commitment. Front Cell Dev Biol. 2021. https://doi.org/10.3389/fcell.2020.611197.

Article  PubMed  PubMed Central  Google Scholar 

Wang X, Yu F, Ye L. Epigenetic control of mesenchymal stem cells orchestrates bone regeneration. Front Endocrinol. 2023;14:1126787.

Article  Google Scholar 

Chen Y, Tan J, Yang C, Ling Z, Xu J, Sun D, et al. Dynamic chromatin accessibility landscapes of osteoblast differentiation and mineralization. Biochimica et biophysica acta (BBA) -. Mol Basis Disease. 2024;1870(2):166938.

Article  CAS  Google Scholar 

Weng Y, Feng Y, Li Z, Xu S, Wu D, Huang J, Wang H, Wang Z. Zfp260 choreographs the early stage osteo-lineage commitment of skeletal stem cells. Nat Commun. 2024;15:10186.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dudakovic A, Camilleri ET, Paradise CR, et al. Enhancer of Zeste homolog 2 (Ezh2) controls bone formation and cell cycle progression during osteogenesis in mice. J Biol Chem. 2018;293:12894–907.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Carrasco ME, Thaler R, Nardocci G, Dudakovic A, Van Wijnen AJ. Inhibition of Ezh2 redistributes bivalent domains within transcriptional regulators associated with WNT and Hedgehog pathways in osteoblasts. J Biol Chem. 2023;299:105155.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dudakovic A, Camilleri ET, Xu F, et al. Epigenetic control of skeletal development by the histone methyltransferase Ezh2. J Biol Chem. 2015;290:27604–17.

Article  CAS  PubMed  PubMed Central  Google Scholar 

James AW, LaChaud G, Shen J, Asatrian G, Nguyen V, Zhang X, Ting K, Soo C. A review of the clinical side effects of bone morphogenetic Protein-2. Tissue Eng Part B: Reviews. 2016;22:284–97.

Article  CAS  Google Scholar 

Lui H, Samsonraj RM, Vaquette C, Denbeigh J, Kakar S, Cool SM, Dudakovic A, Van Wijnen AJ. Combination of BMP2 and EZH2 Inhibition to stimulate osteogenesis in a 3D bone reconstruction model. Tissue Eng Part A. 2021;27:1084–98.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dudakovic A, Samsonraj RM, Paradise CR, et al. Inhibition of the epigenetic suppressor EZH2 primes osteogenic differentiation mediated by BMP2. J Biol Chem. 2020;295:7877–93.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dashti P, Van De Peppel J, Thaler R, Paradise CR, Stein GS, Montecino MA, Van Leeuwen JPTM, Van Der Eerden BJ, Dudakovic A, Van Wijnen AJ. The lysine methyltransferases SET and MYND domain containing 2 (Smyd2) and enhancer of Zeste 2 (Ezh2) co-regulate osteoblast proliferation and mineralization. Gene. 2023;851:146928.

Article  CAS  PubMed 

Comments (0)

No login
gif