CDMP1 promotes type II collagen and aggrecan synthesis of nucleus pulposus cell via the mediation of ALK6. 2020

Z Yang, and X-J Gao, and X Zhao
Department of Orthopaedics, Caoxian People's Hospital, Heze, China. 275262151@qq.com.

Destruction of extracellular matrix (ECM), especially collagen II and aggrecan, is an essential feature of intervertebral disc degeneration (IDD). This project planned to elucidate the role of cartilage-derived morphogenetic protein-1 (CDMP-1) in the collagen II and aggrecan synthesis of nucleus pulposus (NP) cells under the IL-1β induced degeneration. We cultured human primary NP cells in the different concentrations of IL-1β medium and analyzed the CDMP-1 level. Recombinant human CDMP-1 protein was used to co-culture with IL-1β to investigate its effects on collagen II and aggrecan synthesis of NP cells. Additionally, the bone morphogenetic protein type IB receptor (ALK6) gene silenced and upregulated NP cells were used to evaluate the function of ALK6 in the CDMP-1 treated NP cells. Collagen II, aggrecan, MMP9, MMP13, and TIMP4 expression level were analyzed to assess the ECM stability of NP cells. CDMP-1 gene expression decreased in the IL-1β treated NP cells with a dose-dependent. Appropriate CDMP-1 protein supplement contributed to the collagen II and aggrecan production, the suppression of MMP9 and MMP13, and the upregulation of TIMP4. However, the silencing of ALK6 rejected the positive function of CDMP-1 on the collagen II and aggrecan; on the contrary, ALK6 upregulation magnified the CDMP-1 induced collagen II and aggrecan production. CDMP-1 is efficient in promoting the collagen II and aggrecan synthesis of NP cells, which is probably based on the mediation of ALK6.

UI MeSH Term Description Entries
D008297 Male Males
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000070614 Nucleus Pulposus Fibrocartilage inner core of the intervertebral disc. Prolapsed or bulged nucleus pulposus leads to INTERVERTEBRAL DISC DISPLACEMENT while proliferation of cells in the nucleus pulposus is associated with INTERVERTEBRAL DISC DEGENERATION.
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D052005 Bone Morphogenetic Protein Receptors, Type I A subtype of bone morphogenetic protein receptors with high affinity for BONE MORPHOGENETIC PROTEINS. They can interact with and undergo PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II. They signal primarily through RECEPTOR-REGULATED SMAD PROTEINS. Activin Receptor-Like Kinase 3,Activin Receptor-Like Kinase 6,BMP Type I Receptor,BMP Type IA Receptor,BMP Type IB Receptor,BMPR-I Receptors,BMPR-IA Receptor,BMPR-IB Receptor,Bone Morphogenetic Protein Receptor Type I,Bone Morphogenetic Protein Receptor, Type IA,Bone Morphogenetic Protein Receptor, Type IB,Serine-Threonine Protein Kinase Receptor R6,Type I Bone Morphogenetic Protein Receptors,Type IA Bone Morphogenetic Protein Receptor,Type IB Bone Morphogenetic Protein Receptor,Activin Receptor Like Kinase 3,Activin Receptor Like Kinase 6,BMPR I Receptors,BMPR IA Receptor,BMPR IB Receptor,Serine Threonine Protein Kinase Receptor R6
D053674 Aggrecans Large HYALURONAN-containing proteoglycans found in articular cartilage (CARTILAGE, ARTICULAR). They form into aggregates that provide tissues with the capacity to resist high compressive and tensile forces. Aggrecan,Cartilage-Specific Proteoglycan Core Proteins,Cartilage Specific Proteoglycan Core Proteins
D055428 Growth Differentiation Factor 5 A growth differentiation factor that plays a role in early CHONDROGENESIS and joint formation. CDMP-1,Cartilage-Derived Morphogenetic Protein 1,Cartilage-Derived Morphogenetic Protein-1,GDF-5,Cartilage Derived Morphogenetic Protein 1
D024043 Collagen Type II A fibrillar collagen found predominantly in CARTILAGE and vitreous humor. It consists of three identical alpha1(II) chains. Collagen Type II, alpha1 Chain,Collagen Type II, alpha1 Subunit,Collagen alpha1(II),Procollagen Type II,Type II Collagen,Type II Procollagen,Collagen, Type II,Procollagen, Type II

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