Jie Shen, Ph.D.

Assistant Professor
Orthopaedic Surgery

Developmental, Regenerative and Stem Cell Biology Program
Molecular Cell Biology Program
Molecular Genetics and Genomics Program

  • 314 747-2567

  • shen.j@wustl.edu

  • Focused on injury, repair, and regeneration of musculoskeletal tissues with the goal to understand the progenitor cell population, signals, and role of inflammation on tissue injury and regeneration at the cellular and molecular level

Research Abstract:

My current interests span aspects of bone and cartilage research, and are mainly focused on injury, repair, and regeneration of musculoskeletal tissues with the goal to understand the progenitor cell population, signals, and role of inflammation on tissue injury and regeneration at the cellular and molecular level. One of my major focuses is to clarify the epigenetic regulation of bone regeneration in inflammatory diseases. In the United States, approximately 1.6 million bone fractures encounter prolonged healing or non-union each year, among which, the major population bearing with these clinical complications are patients with inflammatory conditions, e.g, elder patients, smoking, diabetic or rheumatoid arthritis (RA) patients. Studies from patients and rodents extensively documented that chronic systemic inflammation activates canonical NF-κB (IKK2) pathway resulting with elevated expression of IL-1β TNFα and other cytokines, which impair the fracture repair process by negatively affecting MPC differentiation, chondrocyte maturation and angiogenesis. Recent epigenome studies from fracture patients revealed differential methylation loci associated with stem cell proliferation and differentiation in human mesenchymal stem cells, suggesting that DNA methylation is involved in fracture repair process. In this regard, we propose to utilize state-of-the-art methodologies to probe the interplay among NF-κB, Dnmt3b and Rbpjjκ.g. conditional Cre/LoxP mutant transgenic mouse models, murine surgical models of bone fracture) and to couple these with in vitro primary cell culture and next-generation sequencing methodology to understand the contribution of epigenetic regulators to the skeletal fracture repair and bone regeneration under inflammatory conditions. This innovative work will provide new mechanistic insights toward understanding the role of inflammation (NF-κB/IKK2), DNA methylation (Dnmt3b) and Rbpjκ as the downstream target during fracture repair. We expect to identify new targets for future development of effective strategies to treat delayed fracture union and non-union.

In addition to skeletal regeneration, the other major focus of my laboratory is to delineate the effect of inflammation on skeletal degenerative disease, such as Osteoarthritis (OA).

Selected Publications:

Ying J, Xu T, Wang C, Jin H, Tong P, Guan J, Abu-Amer Y, O'Keefe R, Shen J. Dnmt3b ablation impairs fracture repair through upregulation of Notch pathway. JCI Insight. 2020 Feb 13;5(3). doi: 10.1172/jci.insight.131816. PubMed PMID: 32051335; PubMed Central PMCID: PMC7098799.

Niu H, Li C, Guan Y, Dang Y, Li X, Fan Z, Shen J, Ma L, Guan J. High oxygen preservation hydrogels to augment cell survival under hypoxic condition. Acta Biomater. 2020 Mar 15;105:56-67. doi: 10.1016/j.actbio.2020.01.017. Epub 2020 Jan 15. PubMed PMID: 31954189; PubMed Central PMCID: PMC7098391.

Duan X, Cai L, Schmidt EJ, Shen J, Tycksen ED, O'Keefe RJ, Cheverud JM, Rai MF. RNA-seq analysis of chondrocyte transcriptome reveals genetic heterogeneity in LG/J and SM/J murine strains. Osteoarthritis Cartilage. 2020 Apr;28(4):516-527. doi: 10.1016/j.joca.2020.01.001. Epub 2020 Jan 14. PubMed PMID: 31945456; PubMed Central PMCID: PMC7108965.

Arra M, Swarnkar G, Ke K, Otero JE, Ying J, Duan X, Maruyama T, Rai MF, O'Keefe RJ, Mbalaviele G, Shen J, Abu-Amer Y. LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis. Nat Commun. 2020 Jul 9;11(1):3427. doi: 10.1038/s41467-020-17242-0. PubMed PMID: 32647171; PubMed Central PMCID: PMC7347613.

Zhou Y, Chen M, O'Keefe RJ, Shen J, Li Z, Zhou J, Zhou X, Mao JJ. Epigenetic and therapeutic implications of dnmt3b in temporomandibular joint osteoarthritis. Am J Transl Res. 2019;11(3):1736-1747. eCollection 2019. PubMed PMID: 30972197; PubMed Central PMCID: PMC6456519.

Xia C, Wang P, Fang L, Ge Q, Zou Z, Dong R, Zhang P, Shi Z, Xu R, Zhang L, Luo C, Ying J, Xiao L, Shen J, Chen D, Tong P, Jin H. Activation of β-catenin in Col2-expressing chondrocytes leads to osteoarthritis-like defects in hip joint. J Cell Physiol. 2019 Aug;234(10):18535-18543. doi: 10.1002/jcp.28491. Epub 2019 Mar 25. PubMed PMID: 30912140; PubMed Central PMCID: PMC6606325.

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. PubMed PMID: 31534049; PubMed Central PMCID: PMC6795381.

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. 2020 Mar;48(3):927-939. doi: 10.1007/s10439-019-02264-7. Epub 2019 Apr 12. PubMed PMID: 30980293; PubMed Central PMCID: PMC6790162.

Last Updated: 2/15/2021 2:58:01 PM

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