Bone development and remodeling:
1. Molecular mechanisms and pathogenesis of osteoporosis, osteoarthritis, intervertebral disc degeneration and defects in fracture healing
2. Genetic mouse models specifically targeting osteoblasts and chondrocytes
3. Osteoblast and chondrocyte biology
4. Bone cell BMP and Wnt signaling
5. Bone cell protein ubiquitination and sumoylation
6. Bone cell micro-RNA regulation

1. Chen D, Ji X, Harris MA, Feng JQ, Celeste AJ, Rosen V, Mundy GR, and Harris SE (1998) Differential roles for BMP receptor type IB and IA in differentiation and specification of mesenchymal precursor cells to osteoblast and adipocyte lineages. J Cell Biol 142:295-305.
2. Nishimura R, Kato Y, Chen D, Harris SE, Mundy GR, and Yoneda T (1998) Samd5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12. J Biol Chem 273:1872-1879.
3. Shi X, Yang X, Chang Z, Chen D, and Cao X (1999) Smad1 interacts with homeodomain DNA binding proteins in BMP signaling. J Biol Chem 274:13711-13717.
4. Mundy GR, Garrett R, Harris SE, Chan J, Chen D, Rossini G, Boyce B, Zhao M, and Gutierrez G (1999) Stimulation of bone formation in vitro and in rodents by statins. Science 286:1946-1949.
5. Zhao M, Harris SE, Horn D, Geng Z, Nishimura R, Mundy GR, and Chen D (2002) BMP receptor signaling is necessary for normal murine postnatal bone formation. J Cell Biol 157:1049-1060.
6. Garrett IR, Chen D, Gutierrez G, Rossini G, Zhao M, Escobedo A, Kim KB, Hu S, Crews CM, and Mundy GR (2003) Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro. J Clin Invest 111:1771-1782.
7. Zhao M, Qiao M, Oyajobi B, Mundy GR, and Chen D (2003) E3 ubiquitin ligase Smurf1 mediates core-binding factor alpha 1/Runx2 degradation and plays a specific role in osteoblast differentiation. J Biol Chem 278:27939-27944.
8. Feng JQ, Xing L, Zhang J, Zhao M, Horn D, Chan J, Boyce BF, Harris SE, Mundy GR and Chen D (2003) NF-κB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro. J Biol Chem 278:29130-29135.
9. Zhao M, Qiao M, Harris SE, Oyajobi BO, Mundy GR, and Chen D (2004) Smurf1 inhibits osteoblast differentiation and bone formation in vitro and in vivo. J Biol Chem 279:12854-12859.
10. Ye L, Mishina Y, Chen D, Huang H, Dallas SL, Dallas M, Kunieda TW, Tsutsui T, Boskey A, Bonewald LF and Feng JQ (2005) Dentin matrix protein 1 (Dmp1) deficient mice display severe defects in cartilage formation responsible for a chondrodysplasia-like phenotype J Biol Chem 280:6197-6203.
11. Li TF, Darowish M, Zuscik MJ, Chen D, Schwarz EM, Rosier RN, Drissi H, O'Keefe RJ (2005) Smad3-deficient chondrocytes have enhanced BMP signaling and accelerated differentiation. J Bone Miner Res 21:4-16.
12. Young N, Mikhalkevich N, Yan Y, Chen D, and Zheng WP (2005) Differential regulation of osteoblast activity by Th cell subsets mediated by parathyroid hormone and IFN-gamma. J Immunol 175:8287-8295.
13. Cao X and Chen D (2005) The BMP signaling and in vivo bone formation. Gene 357:1-8. Review
14. Boyce BF, Xing L, and Chen D (2005) Osteoprotegerin, the bone protector, is a surprising target for β-catenin signaling. Cell Metab 2:344-345. Preview
15. Shen R, Chen M, Wang Y, Kaneki H, Xing L, O’Keefe RJ and Chen D (2006) Smad6 interacts with Runx2 and mediates Smurf1-induced Runx2 degradation. J Biol Chem 281:3569-3576.
16. Kaneki H, Gao R, Chen D, Yao Z, Schwarz EM, Zhang YE, Boyce BF, and Xing L (2006) TNF promotes Runx2 degradation through up-regulation of Smurf1 and Smurf2 in osteoblasts. J Biol Chem 281:4326-4333.
17. Shen R, Wang X, Drissi H, Liu F, O’Keefe RJ, and Chen D (2006) Cyclin D1-CDK4 induce Runx2 ubiquitination and degradation. J Biol Chem 281:16347-16353.
18. Li T, Chen D, Wu Q, Chen M, Sheu T, Schwarz EM, Drissi H, Zuscik M, and O’Keefe RJ (2006) TGF-beta stimulates cyclin D1 expression through activation of beta-catenin signaling in chondrocytes. J Biol Chem 281:21296-21304.
19. Zhao M, Qiao M, Harris SE, Chen D, Oyajobi BO and Mundy GR (2006) The zinc finger transcription factor Gli2 mediates bone morphogenetic protein 2 expression in osteoblasts in response to hedgehog signaling. Mol Cell Biol 26:6197-6208.
20. Chen M, Lichtler AC, Sheu T, Xie C, Zhang X, O’Keefe RJ and Chen D (2007) Generation of a transgenic mouse model with chondrocyte-specific and tamoxifen-inducible expression of Cre recombinase. Genesis 45:44-50.
21. Wang Q, Wei X, Zhu T, Zhang M, Shen R, Xing L, O’Keefe RJ, and Chen D (2007) BMP-2 activates Smad6 gene transcription through bone-specific transcription factor Runx2 J Biol Chem 282:10742-10748.
22. Tan X, Weng T, Zhang J, Wang J, Li W, Wan H, Lan Y, Cheng X, Hou N, Liu H, Ding J, Lin F, Yang R, Gao X, Chen D, and Yang X (2007) Smad4 is required for maintaining normal murine postnatal bone homeostasis J Cell Sci 120:2162-2170.
23. Zhu M, Chen M, Lichtler AC, O’Keefe RJ, and Chen D (2008) Tamoxifen-inducible Cre-recombination in articular chondrocytes of adult Col2a1-CreERT2 transgenic mice. Osteoarthr Cartilage 16:129-130.
24. Usui M, Xing L, Drissi H, Zuscik M, O’Keefe RJ, Chen D, and Boyce BF (2008) Murine and Chicken Chondrocytes Regulate Osteoclastogenesis by Producing RANKL in Response to BMP2. J Bone Miner Res 23:314-325.
25. Wu Q, Chen D, Zuscik MJ, O’Keefe RJ and Rosier RN (2008) Overexpression of Smurf2 stimulates endochondral ossification through upregulation of β-catenin. J Bone Miner Res 23:552-563.
26. Chen M, Zhu M, Awad H, Li TF, Sheu TJ, Boyce BF, Chen D, and O’Keefe RJ (2008) Inhibition of β-catenin signaling causes defects in postnatal cartilage development. J Cell Sci 121:1455-1465.
27. Zhu M, Chen M, Zuscik M, Wu Q, Wang Y, Rosier RN, O’Keefe RJ and Chen D (2008) Inhibition of β-catenin signaling in articular chondrocytes results in articular cartilage destruction. Arth Rheum 58:2053-2064. Editorial comments: Inhibition of β-catenin hurts rather than helps in OA. 58:A20 (2008).
28. Li X, Huang M, Zheng H, Wang Y, Ren F, Shang Y, Zhai Y, Irwin DM, Shi Y, Chen D, and Chang Z (2008) CHIP promotes Runx2 degradation and negatively regulates osteoblast differentiation. J Cell Biol 181:959-972.
29. Guo R, Yamashita M, Zhang Q, Zhou Q, Chen D, Reynolds DG, Award H, Yanoso L, Zhao L, Schwarz EM, Zhang Y, Boyce BF, and Xing L (2008) Ubiquitin ligase Smurf1 mediates tumor necrosis factor-induced systemic bone loss by promoting proteasomal degradation of bone morphogenetic signaling proteins. J Biol Chem 283:23084-23092.
30. Wu Q, Kim K-O, Sampson ER, Chen D, Awad H, Puzas JE, Drissi H, Schwarz EM, O’Keefe RJ, Zuscik MJ, and Rosier RN (2008) Induction of an osteoarthritis-like phenotype and degradation of phosphorylated Smad3 by Smurf2 in transgenic mice. Arth Rheum 58:3132-3144. (Cover Image)
31. Zhu M, Tang D, Wu Q, Hao S, Chen M, Xie C, Rosier RN, O'Keefe, RJ, Zuscik M, and Chen D (2009) Activation of β-catenin signaling in articular chondrocytes leads to osteoarthritis-like phenotype in adult β-catenin conditional activation mice. J Bone Miner Res 24:12-21. (Cover Image) Commentary: Regulation of osteoarthritis development by Wnt/β-catenin signaling through the endochondral ossification process. J Bone Miner Res 24:8-11. Medium Coverage: ABC News, Washington Post, US News & World Report, and Forbes
32. Zuscik MJ, Hilton MJ, Zhang X, Chen D and O’Keefe RJ (2008) Molecular targets of stress during chondrogenesis. J Clin Invest 118:429-438. Review
33. Zhao M, Chen D, Zhang J, Wang B, Stephen E. Harris SE, Oyajobi BO, and Mundy GR (2008) Microtubule disassembly in osteoblasts stimulates BMP-2 expression and bone formation. Mol Cell Biol (In press)
34. Zhang M, Xie R, Hou W, Shen R, Wang X, Wang Q, Zhu T, Jonason JH, and Chen D (2008) PTHrP prevents chondrocyte premature hypertrophy by inducing cyclin D1-dependent Runx2 and Runx3 phosphorylation, ubiquitination and proteasome degradation. J Cell Sci (In press)