Regis J. O`Keefe, M.D., Ph.D.

Fred C Reynolds Professor and Chair
Orthopaedic Surgery

Molecular Cell Biology Program
Molecular Genetics and Genomics Program

  • 314 747-8414

  • okeefer@wustl.edu

  • Cartilage research, bone repair, skeletal development, cancer and inflammatory diseases of bone

  • Cartilage research, bone repair, skeletal development, cancer and inflammatory diseases of bone

Research Abstract:

Recently, the O'Keefe laboratory demonstrated that DNA methyltransferase 3b (DNMT3B) expression is abundant in normal articular cartilage, but has markedly reduced in osteoarthritis (OA) cartilage. Using genetic approaches, we have shown that DNMT3B loss of function results in spontaneous OA, while DNMT3B gain of function protects against the development of injury induced OA. Finally, we have found a consensus NFkB binding site in the DNMT3B promoter that suppresses gene expression, thus linking inflammation with reduced DNMT3B, altered
methylation, and development of OA.

Selected Publications:

Shen J, Wang C, Ying J, Xu T, McAlinden A, O'Keefe RJ. Inhibition of 4-aminobutyrate aminotransferase protects against injury-induced osteoarthritis in mice. JCI Insight. 2019 Sep 19;4(18). doi: 10.1172/jci.insight.128568.

Feigenson M, Jonason JH, Shen J, Loiselle AE, Awad HA, O'Keefe RJ. Inhibition of the Prostaglandin EP-1 Receptor in Periosteum Progenitor Cells Enhances Osteoblast Differentiation and Fracture Repair. Ann Biomed Eng. 2019 Apr 12;. doi: 10.1007/s10439-019-02264-7. [Epub ahead of print]

Xu T, Wang C, Shen J, Tong P, O'Keefe R. Ablation of Dnmt3b in chondrocytes suppresses cell maturation during embryonic development. J Cell Biochem. 2018 Jul;119(7):5852-5863. doi: 10.1002/jcb.26775.

Yukata K, Xie C, Li TF, Brown ML, Kanchiku T, Zhang X, Awad HA, Schwarz EM, Beck CA, Jonason JH, O'Keefe RJ. Teriparatide (human PTH1-34) compensates for impaired fracture healing in COX-2 deficient mice. Bone. 2018 May;110:150-159. doi: 10.1016/j.bone.2018.02.001.

Wang C, Abu-Amer Y, O'Keefe RJ, Shen J. Loss of Dnmt3b in Chondrocytes Leads to Delayed Endochondral Ossification and Fracture Repair. J Bone Miner Res. 2018 Feb;33(2):283-297. doi: 10.1002/jbmr.

Wang C, Silverman RM, Shen J, O'Keefe RJ. Distinct metabolic programs induced by TGF-β1 and BMP2 in human articular chondrocytes with osteoarthritis. J Orthop Translat. 2018 Jan;12:66-73. doi: 10.1016/j.jot.2017.12.004.

Last Updated: 1/13/2020 12:59:00 PM

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