Dr. Zhen’s study focuses on revealing the mechanism that underlies subchondral bone pathology during osteoarthritis initiation and progression.
She found that TGFβ activity is aberrantly elevated in the subchondral bone in response to the altered mechanical loading in OA animal model and human subjects. High levels of TGF-beta induced formation of nestin+ mesenchymal stem cell (MSCs) clusters leading to abnormal bone formation accompanied by increased angiogenesis.
Suppressed TGFβ signaling in subchondral bone MSC lineage cells attenuated osteoarthritis progression. Considering osteoarthritis as a disease of the whole joint, Dr. Zhen also studies the biomechanical interplay between subchondral bone and articular cartilage and its role in the development of osteoarthritis.
Zhen G, Wen C, Jia X, Li Y, Crane J, Mears S, Askin F, Frassica F, Chang W, Yao J, Artemov D, Chen Q, Zhao Z, Zhou X, Cosgarea A, Carrino J, Riley L, Sponseller Paul, Wan M, Lu W, Cao X. Inhibition of TGFβ signaling in subchondral bone mesenchymal stem cells prevents onset of osteoarthritis. Nature Medicine. 2013; 19 (6):704-712. PMID: 23685840
Cui Z, Crane J, Xie H, Jin X, Zhen G, Li C, Xie L, Wang L, Bian Q, Qiu T, Wan M, Xie M, Ding S, Yu B, Cao X. Halofuginone attenuates osteoarthritis by inhibition of TGF-β activity and H-type vessel formation in subchondral bone. Annals of the Rheumatic Diseases. 2015 Oct 15. PMID: 26470720
Li C, Zhen G, Chai Y, Xie L, Crane JL, Farber E, Farber CR, Luo X, Gao P, Cao X, Wan M. RhoA determines lineage fate of mesenchymal stem cells by modulating CTGF-VEGF complex in extracellular matrix. Nature Communication. 2016 Apr 29;7:11455. PMID: 27126736
Johnson B, Lancaster K, Zhen G, He J, Gupta1 M, Kong Y, Engel E, Krick K, Ju1 A, Fanben Meng F, Enquist L, Jia X, McAlpine M. 3D Printed Anatomical Nerve Regeneration Pathways. Advance Functional Materials. 2015 Oct 21. Volume 25, Issue 39, pages 6205–6217. PMID: 26924958
Zhen G, Cao X. TGFβ Signaling in Joint Homeostasis and Therapeutic Implications for Osteoarthritis. Trends in Pharmacological Sciences. 2014 35(5):227-36. PMID: 22646092