陈棣 男 中国科学院深圳先进技术研究院
1.One of my early research works was focused on BMP signaling and osteoblast differentiation. We cloned Bmp2, Bmp3 and Bmp4 genomic DNAs and cDNAs from different species and investigated function of BMP receptors and BMP signaling molecules Smad1/5. We have determined the role of BMP receptor in osteoblast differentiation and postnatal bone formation. Later we also determined the role of Bmp2 and Bmp4 genes in skeletal development.
2. Runx2 in post-transcriptional regulation. My lab, for the first time identified specific Hect domain E3 ligases, Smurf1 and Smurf2, which recognized the PY motif of Runx2 and mediated Runx2 ubiquitination and proteasome degradation. We also found that Smad6 interacted with Runx2 and enhanced Smurf1-mediated Runx2 degradation. We also found that TNFα promotes Runx2 degradation via inducing Smurf up-regulation in osteoblasts.
3. We have investigated the role of PTH/PTHrP in chondrocyte function and OA development. My lab demonstrated, for the first time, that cell cycle protein cyclin D1/CDK4 induce Runx2 phosphorylation and subsequent ubiquitination/proteasome degradation. We found that PTHrP prevents chondrocyte premature hypertrophy through inducing cyclin D1-dependent Runx2 and Runx3 degradation. We also found that PTH has chondro-protective effect in an experimentally-induced OA mouse model.
4. I have made significant contributions in our understanding of chondrocyte β-catenin signaling in the development of arthritis, especially spondyloarthritis (SpA). We found that β-catenin expression was upregulated in patients with OA and disc degeneration. We generated a mouse model with chondrocyte-specific β-catenin conditional activation, β-catenin(ex3)Col2ER, showing defects in spine, including disc and facet joint, knee joint and temporomandibular joint (TMJ). This mouse model closely resembles SpA phenotype.
5. We found that TGF-β signaling plays a critical role in OA development. Deletion of TGF-β type II receptor gene (Tgfbr2Col2ER) in a conditional KO mice caused time-dependent progression of OA-like phenotype. MMP13 and Adamts5 are key downstream target genes of TGF-β signaling in articular chondrocytes.
6. We have generated a chondrocyte-specific Col2-CreER transgenic mouse model which can be used to delete floxed genes of interest in growth plate and articular chondrocytes and chondrocytes located in other tissues other than long bone. These transgenic mice have been demonstrated a very useful tool for mouse genetic studies. More than 20 papers have been published showing these mice could be used to mediate targeted gene deletion in chondrocytes.
7. Axin1 and Axin2 are key negative regulators of β-catenin signaling. Deletion of Axin2 has a high bone mass phenotype. We have generated Axin1 conditional allele and will determine the role of Axin1/Axin2 in skeletal pattern formation and in the development of genetic bone diseases.
8. We have investigated the role of miRNAs regulation in Runx2 expression and found that miR-204/miR-211 play a key role in regulation of Runx2 expression in mesenchymal progenitor cells. Currently we are generated MSC-specific miR-204/-211 double KO mice and determine the role of these miRNAs in OA development.
2014-12-31-今,编委：Oncology and Translational Medicine,
2014-01-01-今,编委：Scientific Reports (Nature Publishing Group),
2013-01-01-今,主编：Journal of Orthopaedic Translation,
2012-01-01-今,编委会成员：Osteoarthritis and Cartilage,
2011-01-01-今,副编委：American Journal of Stem Cells,
2009-01-01-今,编委会成员：Arthritis Research & Therapy,
2009-01-01-今,编委：Chinese Journal of Osteoporosis and Bone Mineral Research,
2008-01-01-今,编委：Journal of Cellular Biochemistry,
2006-01-01-今,编委会成员：Calcified Tissue International,
2005-01-01-今,编委：Journal of Orthopaedic Surgery and Research,