title: FoxC2 Enhances BMP7-Mediated Anabolism in Nucleus Pulposus Cells of the Intervertebral Disc.
abstract: Bone-morphogenetic protein-7 (BMP-7) is a growth factor that plays a major role in mediating anabolism and anti-catabolism of the intervertebral disc matrix and cell homeostasis. In osteoblasts, Forkhead box protein C2 (FoxC2) is a downstream target of BMPs and promotes cell proliferation and differentiation. However, the role FoxC2 may play in degenerative human intervertebral disc tissue and the relationship between FoxC2 and BMP-7 in nucleus pulposus (NP) cells remain to be elucidated. This study aims to investigate the presence and signaling mechanisms of FoxC2 in degenerative human intervertebral disc tissue and NP cells. Western blot and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses were used to measure FoxC2 expression in the NP tissue and cells. Transfections were carried out to measure the effect of FoxC2 on BMP-7-mediated extracellular matrix upregulation. Adenoviral knock-down of Smad1 was performed to investigate the mechanism of BMP-7-induced FoxC2 expression. In degenerative NP tissue, FoxC2 was markedly upregulated and positively correlated with increased disc degeneration. Induction of NP cell proliferation was confirmed by using cell counting kit-8 assay, immunocytochemistry and real-time qRT-PCR for Ki67. FoxC2 led to decreased noggin expression and increased Smad1/5/8 phosphorylation. During combined treatment with BMP-7, FoxC2 greatly potentiated anabolism through synergistic mechanisms on ECM formation. Combination therapy using BMP-7 and FoxC2 may be beneficial to the treatment of intervertebral disc degeneration.
authors.affiliation: Department of Spinal Surgery,The First Hospital of Jilin University, No.71,Xinmin Avenue, Chaoyang District, Changchun, Jilin Province 130021,China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Spinal Surgery,The First Hospital of Jilin University, No.71,Xinmin Avenue, Chaoyang District, Changchun, Jilin Province 130021,China.
authors.forename: Changfeng
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, The First Hospital of Jilin University, No.71, Xinmin Avenue, Chaoyang District, Changchun, Jilin Province 130021, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Spinal Surgery,The First Hospital of Jilin University, No.71,Xinmin Avenue, Chaoyang District, Changchun, Jilin Province 130021,China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Spinal Surgery,The First Hospital of Jilin University, No.71,Xinmin Avenue, Chaoyang District, Changchun, Jilin Province 130021,China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Spinal Surgery,The First Hospital of Jilin University, No.71,Xinmin Avenue, Chaoyang District, Changchun, Jilin Province 130021,China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Department of Spinal Surgery,The First Hospital of Jilin University, No.71,Xinmin Avenue, Chaoyang District, Changchun, Jilin Province 130021,China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002574:Cervical Vertebrae / Q000378:metabolism / Q000473:pathology; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008159:Lumbar Vertebrae / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000099176:Noggin Protein
chemical_list: D055419:Bone Morphogenetic Protein 7; D002352:Carrier Proteins; D051858:Forkhead Transcription Factors; D051898:Smad1 Protein; D000099176:Noggin Protein; C497399:SMAD1 protein, human; C082078:mesenchyme fork head 1 protein
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