Cui Lab

Quanjun Cui, MD.
G.J. Wang Professor of Orthopaedic Surgery and Vice Chair for Research.

As a clinician scientist, Dr. Cui’s research has originally focused on two main aspects: (1) Pathogenesis and treatment of osteonecrosis and (2) Stem cell therapy for osteogenesis.  His research team has found that steroids induce adipogenesis by osteoprogenitor cells and stimulate expression of a fat-specific gene while inhibiting osteogenesis by down-regulating osteoblastic gene expression.  He has proposed that this may be an important mechanism by which osteonecrosis and osteoporosis develops.  The results of this study were published in the Journal of Bone and Joint Surgery, which was selected as an abstract in the Yearbook of Orthopaedics and won the William Harris Award by the Orthopaedic Research Society.  Based on these findings, he studied the effects of lipid-clearing agents on steroid-induced adipogenesis by osteoprogenitor cells and discovered that lovastatin, a HMG CoA reductase inhibitor, can counteract the effect of steroids on adipogenesis and thereby maintain the osteogenic properties of the cell.  Similar findings in an in vivo study with a steroid-treated chicken model for osteonecrosis supported the in vitro data.  His paper entitled “Lovastatin Prevents Steroid-Induced Adipogenesis and Osteonecrosis” was selected for the Otto E. Aufranc Award by the American Hip Society.  His other work includes studies on a multipotent bone marrow cell, which has been transduced with a traceable gene as a marker as well as with growth factor genes.  The results of the study, “The Pathogenesis and Prevention of Steroid-induced Osteonecrosis” received the Nicholas Andry Award from The American Association of Bone and Joint Surgeons and published in Clinical Orthopaedics and Related Research. His recent research activities in this area are focusing on finding therapeutic agents to prevent adipogenesis and apoptosis of stem cell in response to glucocorticoid treatment which is the major contributing factor for osteonecrosis. The research findings were recently published in one of the top orthopaedic research journals, the Journal of Orthopaedic Research, with a manuscript titled “Fullerol antagonizes dexamethasone-induced oxidative stress and adipogenesis while enhancing osteogenesis in a cloned bone marrow mesenchymal stem cell”. They successfully received a NIH R21 grant to continue support their efforts studying potential therapeutic effects of antioxidants on prevention of osteonecrosis and osteoporosis in a rabbit model.

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The delivery of marrow stromal cells with  or without transfection using therapeutic genes may provide a valuable treatment for musculoskeletal diseases such as fractures, osteonecrosis, osteoporosis, and some genetic abnormalities. With the support of an OREF Zimmer Career Development Award, Dr. Cui was able to perform a study on transduction of a mouse and human bone marrow stem cell using plasmid and adenovirus containing both VEGF and BMP-6 genes.  The two growth factors (VEGF and BMP-6) are both translated from a single mRNA due to the presence of IRES (Internal Ribosome Entry Site) between the two coding sequences. Using this vector, transient transduction of a cloned bone marrow stem cell was achieved with high efficiency. The efficacy of osteogenesis and angiogenesis by transfected cells was improved significantly. Along this line of research, Dr. Cui’s research team has received MTF (Musculoskeletal Transplant Foundation) Career Development Award to support a study entitled “An optimal deliverable composite graft for bone repair”; OREF/MTF Research Grant to support another project: “Stem cell-based angiogenic and osteogenic gene therapy to enhance bone defect repair”; and a grant from Arthritis National Research Foundation to support the study: “New strategies for treatment of osteonecrosis using stem cells and growth factors”.

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In collaboration with School of Biomedical Engineering, Dr. Cui’s research team successfully received the Department of Defense (DOD) Idea Development Award to support their study: “Novel Bioactive Coatings to Improve Allograft Incorporation”. The goal of the project was to engineer continuous polymer coatings within the pore network of allograft bone for sustained delivery of bioactive factors that target sphingosine 1-phosphate receptors (S1P). S1P is a pleiotropic autocrine and paracrine signaling phospholipid growth factor that impacts proliferation and migration of endothelial cells, mural cells (i.e. vascular smooth muscle cells and pericytes), and osteoblastic cells through a family of high-affinity G protein-coupled receptors (S1P1-5). They have shown that delivery of S1P receptor agonists from poly(lactic-co-glycolic acid) promotes new bone ingrowth by inducing neovascularization and locally regulating the balance of inflammatory cells and osteoblastic (bone forming) cell recruitment.

As a practicing joint replacement (adult reconstruction) surgeon, Dr. Cui’s clinical research has been focused on outcomes of joint replacement surgery and fracture healing. He hopes to translate cellular and molecular techniques to clinical use so that they can improve treatment outcomes of orthopaedic patients, especially patients with osteoarthritis, osteonecrosis, osteolysis, osteoporosis and non-union fractures.

1. Miller MQ, Dighe A, Cui Q, Park SS, Christophel JJ. Regenerative Medicine in Facial Plastic and Reconstructive Surgery: A Review.   JAMA Facial Plast Surg. 2016 Sep 1;18(5):391-4. doi: 10.1001/jamafacial.2016.0913.
2. Kandahari AM, Yang X, Laroche KA, Dighe AS, Pan D, Cui Q. A review of UHMWPE wear-induced osteolysis: the role for early detection of the immune response. Bone Res. 2016 Jul 12;4:16014. doi: 10.1038/boneres.2016.14. eCollection 2016.
3. Madhu V, Dighe AS, Cui Q, Deal DN. Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells. Stem Cells Int. 2016; 2016:1035374. doi: 10.1155/2016/1035374. Epub 2015 Dec 20. PMID: 26798350 PMCID: PMC4699250
4. Yang X, Chordia MD, Du X, Graves JL, Zhang Y, Park YS, Guo Y, Pan D, Cui Q. Targeting formyl peptide receptor 1 of activated macrophages to monitor inflammation of experimental osteoarthritis in rat. J Orthop Res. 2015 Dec 30. doi: 10.1002/jor.23148. [Epub ahead of print] PMID: 26717557
5. Das A, Fishero BA, Christophel JJ, Li CJ, Kohli N, Lin Y, Dighe AS, Cui Q. Poly(lactic-co-glycolide) polymer constructs cross-linked with human BMP-6 and VEGF protein significantly enhance rat mandible defect repair. Cell Tissue Res. 2015 Oct 16. [Epub ahead of print]. PMID: 26475719
6. Das A, Segar CE, Chu Y, Wang TW, Lin Y, Yang C, Du X, Ogle RC, Cui Q, Botchwey EA. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras. 2015 Jun 14;64:98-107. doi: 10.1016/j.biomaterials. 2015.06.019. [Epub ahead of print] PMID: 26125501
7. Kandahari AM, Yang X, Dighe AS, Pan D, Cui Q. Recognition of Immune Response for the Early Diagnosis and Treatment of Osteoarthritis. J Immunol Res. 2015;2015:192415. Epub 2015 May 3. Review. PMID: 26064995
8. Kovach TK, Dighe AS, Lobo PI, Cui Q. Interactions between MSCs and immune cells: implications for bone healing. J Immunol Res. 2015;2015:752510. doi: 10.1155/2015/752510. Epub 2015 Apr 27. Review. PMID: 26000315
9. Li CJ, Madhu V, Balian G, Dighe AS, Cui Q. Cross-Talk Between VEGF and BMP-6 Pathways Accelerates Osteogenic Differentiation of Human Adipose-Derived Stem Cells. J Cell Physiol. 2015 Mar 9. doi: 10.1002/jcp.24983. [Epub ahead of print]. PMID: 25753222
10. Madhu V, Kilanski A, Reghu N, Dighe AS, Cui Q. Expression of CD105 and CD34 receptors controls BMP-induced in vitro mineralization of mouse adipose-derived stem cells but does not predict their in vivo bone-forming potential. J Orthop Res. 2015 May;33(5):625-32. doi: 10.1002/jor.22883. Epub 2015 Mar 31. PMID: 25728702
11. Fishero BA, Kohli N, Das A, Christophel JJ, Cui Q. Current concepts of bone tissue engineering for craniofacial bone defect repair. Craniomaxillofac Trauma Reconstr. 2015 Mar;8(1):23-30. doi: 10.1055/s-0034-1393724. Epub 2014 Nov 18. Review. PMID: 25709750
12. Yang S, Halim AY, Werner BC, Gwathmey FW, Cui Q. Does osteonecrosis of the femoral head increase surgical and medical complication rates after total hip arthroplasty? A comprehensive analysis in the United States. Hip Int. 2015 May 26;25(3):237-44. doi: 10.5301/hipint.5000224. Epub 2015 Feb 18. PMID: 25704263
13. Yang X, Li CJ, Wan Y, Smith P, Shang G, Cui Q. Antioxidative fullerol promotes osteogenesis of human adipose-derived stem cells. Int J Nanomedicine. 2014 Aug 20;9:4023-31. doi: 10.2147/IJN.S66785. eCollection 2014.
14. Madhu V, Li CJ, Dighe AS, Balian G, Cui Q. BMP-Non-Responsive Sca1+CD73+CD44+ Mouse Bone Marrow Derived Osteoprogenitor Cells Respond to Combination of VEGF and BMP-6 to Display Enhanced Osteoblastic Differentiation and Ectopic Bone Formation. PLoS One. 2014 Jul 21;9(7):e103060. doi: 10.1371/journal.pone.0103060. eCollection 2014.
15. Schaffer JC, Adib F, Cui Q. Intraoperative fat embolism during core decompression and bone grafting for osteonecrosis of the hip: report of 3 cases and literature review. Am J Orthop (Belle Mead NJ). 2014 Jun;43(6):275-9.
16. Citak M, Argenson JN, Masri B, Kendoff D, Springer B, Alt V, Baldini A, Cui Q, Deirmengian GK, del Sel H, Harrer MF, Israelite C, Jahoda D, Jutte PC, Levicoff E, Meani E, Motta F, Pena OR, Ranawat AS, Safir O, Squire MW, Taunton MJ, Vogely C, Wellman SS. Spacers. J Orthop Res. 2014 Jan;32 Suppl 1:S120-9. doi: 10.1002/jor.22555.
17. Liu Q, Cui Q, Li XJ, Jin L. The applications of buckminsterfullerene C60 and derivatives in orthopaedic research. Connect Tissue Res. 2014 Apr;55(2):71-9. doi: 10.3109/03008207.2013.877894. Epub 2014 Jan 24.
18. Yang X, Ebrahimi A, Li J, Cui Q. Fullerene-biomolecule conjugates and their biomedicinal applications. Int J Nanomedicine. 2014;9:77-92. Epub 2013 Dec 18.
19. Barrack RL, Berend KR, Cui Q, Fehring TK, Della Valle CJ, Gehrke T, Lombardi AV Jr, Mont MA, Parvizi J, Springer BD. Cement Spacers in Periprosthetic Joint Infection. Clin Infect Dis. 2013 Apr 9. [Epub ahead of print], PMID: 23537904

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