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

OBJECTIVE

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.

PATIENTS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

CDMP-1 is efficient in promoting the collagen II and aggrecan synthesis of NP cells, which is probably based on the mediation of ALK6.