title: SOX9 directly Regulates CTGF/CCN2 Transcription in Growth Plate Chondrocytes and in Nucleus Pulposus Cells of Intervertebral Disc.
abstract: Several lines of evidence indicate that connective tissue growth factor (CTGF/CCN2) stimulates chondrocyte proliferation and maturation. Given the fact that SOX9 is essential for several steps of the chondrocyte differentiation pathway, we asked whether Ctgf (Ccn2) is the direct target gene of SOX9. We found that Ctgf mRNA was down-regulated in primary sternal chondrocytes from Sox9(flox/flox) mice infected with Ad-CMV-Cre. We performed ChIP-on-chip assay using anti-SOX9 antibody, covering the Ctgf gene from 15 kb upstream of its 5'-end to 10 kb downstream of its 3'-end to determine SOX9 interaction site. One high-affinity interaction site was identified in the Ctgf proximal promoter by ChIP-on-chip assay. An important SOX9 regulatory element was found to be located in -70/-64 region of the Ctgf promoter. We found the same site for SOX9 binding to the Ctgf promoter in nucleus pulposus (NP) cells. The loss of Sox9 in growth plate chondrocytes in knee joint and in NP cells in intervertebral disc led to the decrease in CTGF expression. We suggest that Ctgf is the direct target gene of SOX9 in chondrocytes and NP cells. Our study establishes a strong link between two regulatory molecules that have a major role in cartilaginous tissues.
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.|Department of Genetics, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Chun-do
authors.initials: CD
authors.lastname: Oh
authors.affiliation: Department of Genetics, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Yasuda
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.|Department of Orthopaedics &Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Genetics, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Henry
authors.affiliation: Department of Genetics, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Xue
authors.affiliation: Department of Genetics, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: de Crombrugghe
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D055513:Connective Tissue Growth Factor / Q000235:genetics* / Q000378:metabolism; D005121:Extremities; D017353:Gene Deletion; D006132:Growth Plate / Q000166:cytology*; D006801:Humans; D018345:Mice, Knockout; D000070614:Nucleus Pulposus / Q000166:cytology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055758:SOX9 Transcription Factor / Q000378:metabolism*; D013249:Sternum / Q000166:cytology
chemical_list: D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; D055513:Connective Tissue Growth Factor